This publication is Open Access under the license indicated. Learn More
ACS Editors' Choice® is a collection designed to feature scientific articles of broad public interest. Read the latest articles
特色文章
探索反应途径和化学转化网络
点击复制文章链接Article link copied!EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
点击复制文章链接Article link copied!
- 格雷戈尔·N·西姆Gregor N. SimmLaboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, SwitzerlandMore by Gregor N. Simm
- 阿兰·C·瓦歇Alain C. VaucherLaboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, SwitzerlandMore by Alain C. Vaucher
- 马克斯·雷耶尔*Markus Reiher*M. Reiher. E-mail: markus.reiher@phys.chem.ethz.chLaboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, SwitzerlandMore by Markus Reiher
摘要
点击复制章节链接Section link copied!
为了研究化学反应网络，识别所有相关中间体和基本反应是强制性的。存在许多高效的算法方法，可以自动进行探索。这些方法在应用范围、探索的完整性以及所需启发式和人工干预的程度上有所不同。在此，我们根据这些标准描述和比较了不同的方法。讨论了利用化学启发式、人机交互和物理严谨性的未来方向。
版权所有 © 2018 美国化学学会
1. 简介
点击复制章节链接Section link copied!
对一个化学系统的详细分析，需要了解所有相关的中间体和连接它们的潜在能量表面（PES）上的基本反应。对所有反应途径的深入了解，使得人们可以在给定一组初始条件（例如，反应物及其浓度、温度和压力）的情况下研究系统的演变，并提出原始反应物的衍生物以避免不希望的副反应。使用量子化学方法手动探索复杂的反应机制既慢又容易出错。此外，由于 PESs 的高维性，彻底的探索通常是不切实际的。然而，为了合理化不希望的副产物或分解反应的形成，需要揭示意外的反应途径。
复杂的反应机理在化学中普遍存在。例如，它们是过渡金属催化的基础，(1)聚合反应，(2)细胞代谢，(3)酶催化（例如，参考文献(4)和(5)），表面化学（例如，参考文献(6−12)），以及环境过程(13)，并且是系统化学的目标。(14)了解特定化学过程的全部化合物和基本反应对于在原子层面上理解它是必不可少的。尽管许多化学反应导致一个主要产物的选择性生成，(15)通常，多种反应途径相互竞争。各种副产物可能由反应物种（如自由基、不饱和价态物种、带电反应物、强酸和强碱等）或通过光、高温或增加压力填充的高能（电子或振动）状态产生。
一些关于反应途径探索的优秀评论已经存在（参见参考文献<16>和<17>）。然而，我们在这里的概述有不同的重点，并且也扩展了先前评论中涵盖的文献。我们将用于探索 PESs 的众多策略分为三类（一些协议结合了多个类别的策略），如图 1 所示。
第 1 类：从 PES 上的一个点（如左图中的绿色区域所示图1）开始，通过依赖局部曲率信息发现新的 TS 和中间体。此过程会重复（可能在多个方向上）直到探索完所有（相关的）PES 驻定点。
第 2 类：从最低能量结构开始，通过应用启发式方法（如图中直线所示，由化学规则指导）探索 PES（例如，新的中间体或近似的过渡态）。这包括，例如，制定基于图的转换规则或应用人工力推动反应基团相互靠近。一旦找到新的中间体，就可以搜索连接它到起始结构的最低能量路径（MEP）。
第 3 类：人类（化学）知识和直觉的优势可以与超快速计算机模拟相结合，在交互式环境中有效地探索 PES 的中间体和过渡态（图1，右）。这一类别在之前的综述中很少被考虑，这就是为什么我们在这里对其进行了深入讨论。
图 1
图 1. PES 探索的一般策略。左：利用 PES 上的局部曲率信息来识别 TSs 和产物。中：通过应用启发式方法识别新的中间体。右：交互式探索中间体和 TSs。在后两种基于启发式和交互式探索的情况下，需要事后细化路径以获得 MEPs。一个高效的探索方案可以结合不同类别的策略。
对于化学过程的准确描述，不仅要考虑键断裂和键形成转化，还必须探索每个中间体的构象空间。这对于准确描述化合物的热力学性质（例如，吉布斯自由能）以及存在多个连接相同构象异构体的 MEPs 的反应尤其重要。通常，上述所有探索策略都可以用来定位构象异构体。然而，需要注意的是，与键断裂或键形成转化不同，在大多数实际应用中，构象之间的过渡态（TSs）并不感兴趣，因为反应的时间尺度可以假设长于构象达到平衡所需的时间。关于构象生成最近综述，请参阅参考文献(18)。
在接下来的三个部分中，我们回顾了分配给三个类别的算法。这些方法在自动化程度（对于大型反应网络而言尤其关键）、所需启发式策略的数量以及探索的完整性程度上有所不同。涉及少量或无启发式策略的方法往往以更系统的方式探索势能面。然而，它们通常受限于计算需求。相比之下，启发式方法可以有效地研究更大的化学系统，尽管必须小心谨慎，以免通过关于系统反应性的强烈假设而牺牲探索的彻底性。
2. 第 1 类：利用曲率信息
点击复制章节链接Section link copied!
手动构建近似过渡态候选者的过程缓慢、繁琐且非常不系统。因此，最近的研究主要集中在提供更流畅和系统的过渡态定位方法。Ohno 和 Maeda 在一种称为非谐向下畸变（ADDF）的策略中，利用了势能面上的曲率信息。当最小结构以垂直于势能等高线的方向发生畸变时，可以找到反应路径（MEPs）。因此，通过 ADDF 探索的路径非常接近从内禀反应坐标计算得到的路径。对新生成的中间体重复应用 ADDF 可以得到所有相关的 MEPs。ADDF 已成功应用于甲醛、丙炔和甲酸等小分子的反应。最近，Satoh 等人(24)通过仅使用 ADDF 追踪低过渡态能垒，系统地探索了d-葡萄糖的构象转变。
为了解决 ADDF 的局限性，梅田、森口及其同事开发了人工力诱导反应（AFIR）方法。AFIR 通过施加人工力将反应物推在一起来克服分子间活化能。在此偏置力下进行优化时，最大能量点接近真实过渡态。AFIR 已成功应用于克莱森重排、钴催化的加氢甲酰化反应、醇醛缩合反应以及比金利反应。算法的一个后果是，在找到所有相关途径之前，需要采样两种反应物的许多随机初始取向。此外，通常需要人工输入来选择反应分子对，以避免组合爆炸并处理产生的大量数据。
另一种从反应系统的一些构型出发探索潜在能量表面的系统方法是反应分子动力学（MD）模拟，在这种模拟中，通过牛顿运动方程求解原子核或原子的运动，以探索和采样在由预定义的热力学系综施加的约束下可访问的构型空间的一部分。力要么被计算为经典力场势能模型的负梯度，要么是使用近似量子化学方法（通常来自半经验或密度泛函理论）评估的电子能（在从头算MD）的负梯度，对于需要力的构型，该力用于轨迹传播。为了增加反应发生的可能性，模拟的温度和压力通常需要增加，这反过来又导致在常见实验室条件下不太可能发生的转变频繁发生。
反应性从头分子动力学在研究复杂化学反应方面的能力，以原初的乌雷-米勒实验为例得到了证明。由于配置空间可能非常大，包括反应中所有化学物种的多个副本，进行第一性原理计算的计算成本会迅速增长。通过应用反应性经典力场可以克服这个问题（参见最近综述，见参考文献(31−33)）。不幸的是，除了精度降低外，力场参数通常不会适用于任何类型的系统，这限制了它们的适用性。因此，混合量子力学-分子力学方法经常被应用于探索具有许多自由度的复杂系统的反应途径，如酶促反应（参见参考文献(37−42)和 Senn 和 Thiel 的综述(43−45)）。
自然地，采用经典和从头算力场的 MD 模拟可以应用于采样构象自由度。对于具有许多自由度的系统（例如蛋白质），需要使用局部提升(46)或元动力学(47)等增强采样技术（参见参考文献(48)和(49)）。最近的研究进展已在参考文献(50−52)中综述。这些方法是最复杂和耗时最多的构象采样方法之一。(53)基于蒙特卡洛（MC）模拟退火的方法通常比 MD 方法更快。(54−56)通过采样低频本征模态，它们比 MD 模拟需要更少的计算工作量。MD 和 MC 方法在高通量设置中计算成本过高。
2013 年，刘及其同事提出了随机表面行走（SSW）方法来探索 PESs。该方法基于偏置势驱动的动力学和 Metropolis MC 采样。通过随机生成的位移模式和随后构建的偏置势，将平衡点扰动到新的配置。例如，SSW 方法被应用于预测复杂富勒烯的结构(58)、相变(59)，以及研究环氧丙烷的水解和β-d-吡喃葡萄糖的分解。(60)
马丁内斯-努涅斯及其同事开发了一种称为 TS 搜索的化学动力学模拟方法（TSSCDS），(61−65)该方法通过使用半经验量子化学方法进行高能动力学模拟，以诱导反应以高速率发生。通过增加振动模式来增加 TS 被克服的速率。对于大型系统，由于它们的振动模式数量庞大，需要手动干预来引导模拟进入感兴趣的方面。通过模拟生成的轨迹随后进行后处理，并识别出成键和断键事件。从轨迹中提取 TS 猜测，并使用半经验或密度泛函方法进行细化。TSSCDS 方法成功应用于涉及丙烯腈、甲醛和甲酸的反应，以及钴催化的研究。
通常，通过利用 Hessian 信息（即势能相对于核坐标的二阶导数）来对近似 TS 候选体进行细化。为了获得表示反应坐标的常规模式，需要 TS 猜测结构的 Hessian。Eigenvector following（EVF）(66−72)是这种方法的突出例子，如果 TS 猜测结构接近真实 TS，则将是可靠的。对于大分子，即使 Hessian 被近似，完整的 Hessian 计算也将变得计算上要求很高或甚至不可行。因此，已经开发出几种算法来规避完整 Hessian 的计算。Broyden(73)引入了一种准牛顿-拉夫森方法，该方法仅从梯度中构建一个近似的 Hessian，然后通过优化过程中获得的中间点的梯度进行更新。其他方法包括 Munro 和 Wales(74)提出的方案，这些方案避免了 Hessian 的完整对角化，Lanczos 子空间迭代方法(75)和 Davidson 子空间迭代算法(76−79)。
惠勒及其同事开发了一个名为 AARON（用于新催化剂的自动反应优化器）的计算工具包，通过将新催化剂的关键原子映射到基于模型催化剂之前计算的反应过渡态结构中相应原子的位置来构建初始 TS 结构。然后，AARON 执行一个由约束和非约束优化组成的计算协议，以产生优化的 TS 结构。AARON 成功应用于双齿路易斯碱催化的烯丙基化和丙炔基化反应。
3. 第二类：通过化学启发式进行结构跳跃
点击复制章节链接Section link copied!
探索仅基于单个势能面（PES）曲率信息的探索策略通常不适用于具有许多自由度的复杂化学系统以及需要多个 PES 来描述的活性系统，因为这些系统涉及多个步骤，有进入的反应物和产生的副产物。从最小结构开始，应用启发式方法快速识别潜在产物可能更有效，然后搜索连接它们的过渡态（MEP）。如果已知一个基本反应的两个端点，可以应用插值方法（例如，参见参考文献(80)）和字符串方法(78,81−91)来定位连接它们的 MEP。
化学概念知识可用于快速识别与起始结构通过基本反应相连的潜在中间体，特别是在已知与所研究反应系统相关的反应机理类型的情况下。例如，从反应数据库或化学启发式方法中，可以制定并应用转换规则到反应分子的图表示中。这些规则源于键级和价的概念，因此最适合有机化学。1994 年，Broadbelt 及其同事通过引入一种称为 Netgen 的方法，开创了这种方法。分子中原子的三维排列被转化为一种图结构，其中原子和键分别由节点和边表示。这产生了可以通过表示化学变换的矩阵操作来操作的邻接矩阵。通过得到的邻接矩阵，生成新的原子三维排列。 通过反复应用这些转换规则，新的分子被添加到参与全球机制的中间体列表中。在 Broadbelt 的原始工作中，未识别出基本步骤，因此需要使用 Evans–Polanyi 原理来估计活化能垒。 (95)
在类似的精神下，格林及其同事开发了一个名为反应机理生成器（RMG）的软件包。在克服布罗德贝尔特方法所展示的挑战方面采取了众多步骤。特别是，通过量子化学计算估计动力学参数，以排除只有通过具有高活化能垒的过渡态才能达到的产物。RMG 被用于自动映射甲烷热解和正丁醇热解的机理，以及正己烷蒸汽裂解的机理。此外，格林和韦斯特小组成功地将 RMG 应用于各种复杂系统。与 Netgen 类似，RMG 最终受限于键级和价的概念的应用。
格林及其同事开发了一种方法，该方法将图变换和路径细化算法相结合，以找到反应途径。最近，他们通过应用伯尼算法（108-110）以及冻结字符串法、单端和双端增长字符串法以及 AFIR 方法，研究了最简单的γ-酮过氧化氢，3-羟基丙醛的反应网络。
最近，金及其同事利用化学启发式方法快速搜索反应途径。通过应用分子图和反应网络分析，他们探索了一个所谓的最小反应网络，该网络由可以在固定数量的键断裂和形成反应中从起始结构到达的中间体组成。该最小网络经过量子化学计算，以确定动力学上最有利的反应途径。他们将这种方法应用于恢复 Claisen 酯缩合和钴催化的加氢甲酰化反应的接受机制。
ZStruct 方法由 Zimmerman 开发，利用连通图来识别在形成或断开连接时可达的潜在中间体。中间体随后通过双端 MEP 搜索和增长字符串方法进行搜索。ZStruct 的一个局限性是要求两个反应物需要对齐，以便反应复合物接近 MEP。因此，这种方法最适合于分子内反应。此外，如果两个中间体通过两个基本反应连接，ZStruct 将难以找到过渡态。尽管存在缺点，ZStruct 揭示了一个意外的副反应，该反应阻碍了基于 Ni 的 C-H 官能化催化剂。此外，还用 ZStruct 研究了其他几个（催化）反应。最近，Dewyer 和 Zimmerman 解决了 ZStruct 的局限性，并开发了 ZStruct2。在 ZStruct2 中，反应物预先对齐以采样所谓的驱动坐标，这些坐标描述了预期的基本反应。 ZStruct2 已成功应用于研究过渡金属催化剂。 (128−131)
在 Habershon 的方法中，(132,133)连通图描述中间体。通过在可以更新以适应连通图变化的哈密顿量上进行的动力学模拟来检查反应途径。轨迹被处理，并精炼出独特的途径。与 Green 及其同事开发的方法相比，Habershon 的方法以运行动力学模拟为代价，更广泛地探索了势能面。
西方及其同事展示了一种使用群加性方法预测过渡态结构的创新方法。 (111) 通过分子群值估计过渡态中反应原子的距离，以便通过距离几何（DG）——一种将在下文讨论的随机方法——构建一个近似的过渡态。然后，使用标准电子结构方法优化估计的过渡态结构。
Aspuru-Guzik 及其同事开发了一种基于形式键级的方法来模拟原生物反应。而不是具体编码基本反应，转换规则基于有机化学中流行的概念，通常表示为箭头推进，并估计了活化能垒（在参考文献(112−114)中通过采用 Hammond 假设）。
虽然计算效率高，基于图的描述符依赖于价的概念，这可能在许多有机分子中表现良好，但对于包含具有复杂电子结构的物种（如过渡金属簇）的系统可能失败。此外，为了确保使用这种方法进行彻底的探索，需要保证变换规则集的完整性。然而，对于任意未知化学系统，这不能得到保证。因此，人们将局限于已知的化学变换，这可能会阻碍新化学过程的发现。因此，我们追求一种更通用的基于第一性原理启发式方法，该方法适用于任何分子系统，包括含有过渡金属的系统。我们方法的一般适用性是由于所有启发式规则都是来自对分子组成无知的电子波函数。
为了探索 PES，我们从与基本反应步骤相关的高能结构开始。为此，根据从概念电子结构理论推导出的规则生成反应复合物的分子结构。(138−140)随后，通过量子化学方法对其进行优化，以产生新兴反应网络的稳定中间体。(141)然后，通过某种结构相似性度量，自动检测该网络中可能通过基本反应相互关联的中间体对，并对连接的 TS 进行自动搜索。与其它方法相比，我们的方法不依赖于化学键和价的概念。相反，反应位点是通过依赖于从电子波函数计算出的反应性度量来检测的。该协议已在名为Chemoton（以 Gánti 提出的关于活系统功能的理论命名）的软件中实现。(142) 我们通过 Yandulov-Schrock 复合物（143,144）的合成氮固定示例展示了我们方法的能力，其中我们能够识别出导致副反应和分解反应的数千个质子化结构，这些反应解释了催化剂的低周转数。我们还研究了原生物反应，以阐明早期糖形成的不同途径，通过构建一个前所未有的规模反应网络。
我们的方法具有额外的显著特征，这些特征被整合进来，使得量子化学探索成为与实验动力学研究相媲美的水平。为了应对结构组合爆炸的问题，我们将探索与显式动力学建模相结合(148)，以避免在反应条件下动力学上无法到达的构型空间区域浪费计算资源（在我们的原始实现(141)中，我们已为此目的应用了简单的能量截止）。对于特定的探索问题（例如，那些纯粹是有机化学性质的），我们可以利用快速半经验模型，为此我们实现了一个独立的程序，该程序为所有主要模型提供能量和梯度。(149)然而，我们还开发了一种通用的半经验方法，它可以处理过渡金属复合物，因为它通过在线参数化来忽略双原子差分重叠近似，从而利用计算优势，对更精确的计算参考进行计算，这些计算对于类似结构的序列是可靠的。 在努力最大限度地利用快速（因此，准确性较低）方法的过程中，最重要的是能够将误差分配给近似电子结构和物理化学模型，以便从第一性原理水平到动力学模型的速率常数和浓度通量的无缝不确定性量化。我们证明了快速半经验方法和密度泛函方法可以通过与在自动确定结构时获得的从头算参考数据进行比较来校准。为此，我们利用了机器学习方法的置信区间（以高斯过程回归为例）。值得注意的是，我们没有对机器学习模型进行参数化（这可能需要太多数据才能足够可靠），而是仅利用了这些模型中误差估计可用的特性。
最后，我们再次需要解决构象柔性问题，这为从一个化合物到达另一个化合物开辟了许多途径。存在几种探索构象的有效方法，这些方法与第二种探索策略相关。DG 方法随机生成一组原子坐标，这些坐标与一组原子间距离约束进行优化。生成的构象通常使用分子力学力场或量子化学方法进行优化，以提供候选构象。DG 方法的实现可以在《DG-AMMOS》和《RDKit》中找到。(156) (157)
为了减少需要探索的构象空间，通常会引入所谓的刚体转子近似，其中保持键长和键角固定，以便仅采样扭转自由度。遗传算法是一类用于在《Balloon_GA》中实现的大范围扭转角空间随机采样的突出方法，但蒙特卡洛算法也已被用于扭转角的随机采样。然而，随机方法的一个一般问题是可能会错过相关的（即可访问的）构象。因此，所需的采样量是未知的。依赖于刚体转子近似的系统构象生成方法试图枚举分子所有可能的扭转自由度。然而，基于起始构象以蛮力方式对所有可能的扭转角进行系统枚举将导致候选构象的组合爆炸。基于规则的构象生成器限制了它们探索的构象空间。 这些规则通常来源于对数据库中固态结构扭转角度的分析，例如蛋白质数据库(161)或剑桥结构数据库(162,163)。
我们注意到，尽管对于后续动力学模型的重要性不言而喻，但过渡态结构的构象生成似乎是一个难以解决的问题。尽管可以使用讨论过的方法生成（或采样）某些过渡态结构的构象，但这可能导致优化后出现不同的过渡态结构。因此，如何将这些结构正确地纳入一个从一种化合物到另一种化合物的基元步骤的绝对速率理论计算中并不明显。对于过渡态周围反应系统的构象自由度，这尤其困难。
4. 第三类：交互式转向
点击复制章节链接Section link copied!
人类化学直觉和计算机模拟可以形成一个封闭的反馈循环，以有效地探索 PES 上的特定感兴趣区域。这种方法不需要制定启发式转换规则，而是基于人类洞察力和局部斜率信息。交互式科学计算在很早的时候就解决了不同的人类感官问题。在 20 世纪 70 年代初，就提出了将计算机模拟与触觉相结合的第一步。这些概念研究探讨了与计算机进行触觉通信如何增强人机共生。威尔逊和他的同事们预测，交互性和能够感受模拟的可能性在化学领域将有助于更好地理解分子结构和分子相互作用。自那时以来，将交互式沉浸到虚拟分子世界中一直被视为研究和教学的一个引人入胜的方法。 (167,168) 然而，病毒传播尚未发生 (169)，因为用于虚拟和混合现实的人机交互的硬件设备的新设计仍在持续开发中。预计在未来，随着商品设备变得容易且便宜，它们在越来越受欢迎的电脑游戏中所需的，情况可能会发生变化。
交互可以通过运行时修改模拟参数或通过操作模拟系统中的原子或分子来实现。沉浸感往往可以促进和实现交互，因此，许多努力都投入到设计尽可能沉浸式的框架中，这通常需要专用硬件。沉浸感意味着视觉反馈，并且可能通过触觉（触觉）反馈来补充。一方面，视觉反馈通常通过在（计算机）屏幕上以三维形式表示模拟的分子系统来实现。更高级的设置是通过虚拟现实或增强现实实现的，涉及如洞穴自动虚拟环境（CAVE）(170)或头戴式显示器（HMDs）(171,172)等剧院环境。交互式模拟通常使用商用计算机鼠标、三维鼠标、跟踪和记录运动的传感器或手柄控制器来控制。另一方面，触觉反馈是通过结合三维位置输入和力反馈的设备实现的。 在化学相关应用中，这些设备允许选择原子或分子，在空间中移动它们，并提供由操作产生的力反馈。一些设备不仅考虑了位置自由度的三维，还考虑了被操作物体的旋转的三维。在分子环境中实现逼真的触觉反馈已被深入研究，通常取决于目标应用领域。(173−180)在虚拟环境中实现平滑的视觉沉浸通常需要 60 赫兹的更新率，(181)而触觉更敏感，需要大约 1 千赫兹的 10 到 20 倍刷新率。 (182,183)除了视觉和触觉反馈外，一些应用还针对听觉感官，(170,184−187)并且显然语音控制作为输入辅助也可以通过减少输入和结构修改时的延迟来增强交互性和沉浸感。
4.1. 经典模拟中的交互式方法
由于交互性需要快速进行物理属性计算（例如能量和力），分子力学方法，即具有硬编码力场的牛顿力学，是分子模拟的第一个目标，因为物理量易于评估。一个突出的例子是分子对接。受体和配体之间结合位点的可能性众多，以及实现自动算法确定它们的挑战，促使交互式方法利用人类定位合理候选者的能力。项目 GROPE（188,189）针对基于静电和范德华相互作用的相互作用蛋白进行研究，并允许操作者使用六维触觉设备操纵分子，以探索受体和配体之间的相互作用。1997 年，在 CAVE 环境中，交互式分子对接与遗传算法在 Stalk 系统中相结合。它不仅提供了在虚拟现实中可视化遗传算法搜索的可能性，还可以暂停搜索并将配体移动到另一个构象以继续搜索。 然而，需要大量用户研究来证明交互式操作相对于传统计算协议的明显优势，(189,191,192)后来的一些研究表明，触觉反馈在分子对接中的有用性，以及算法和技术改进。 (176,185,193−203)然而，我们注意到，特别是在对接研究中，触觉指针设备并不完全令人信服，因为（i）范德华相互作用较弱，几乎无法让人感觉到主客体之间的吸引力，直到撞到排斥壁的r–12项，以及（ii）如此大量的弱接触几乎无法用低维输入/输出设备正确处理。
在 20 世纪 90 年代，为了在分子动力学模拟中引入人工力，开发了引导分子动力学（SMD）(204)。这使得能够进行原子力显微镜实验的计算研究，并且很快被应用于研究罕见事件。(205−208) 另一个驱动力是 Jarzynski 定理(209)，它将系统在非平衡状态下所做的功与平衡状态起点和终点之间的自由能差异联系起来（尽管这需要缓慢作用的力和对互补自由度的广泛采样）。此外，SMD 中的人工力是在模拟之前预先定义的，并且在模拟过程中不能改变。在运行时改变它的愿望是交互式分子动力学背后的一个动机。(210−212) 最初的方法包括间歇性地更改模拟参数或通过图形用户界面添加用户指定的力。 (172,213,214) 随着计算能力的提升，交互式模拟变得越来越沉浸式，很快在 CAVE 环境中(184)或使用专用硬件如 HMDs(171,172)或触觉设备(215,216)中得到了应用。近年来，人们一直在努力为虚拟现实中的交互式分子动力学设计新的框架(192,217−219)，并使交互式分子动力学在通用硬件上具有更广泛的应用性(186,220)。此外，交互式分子动力学最近还与在图形处理单元上执行的量子化学方法相结合(221)。然而，这种交互式从头开始MD 却受到迭代轨道优化周期收敛问题的困扰，最终破坏了沉浸感（以下将进一步讨论此类问题）。
另一个计算化学中交互式方法的重要应用是化学结构的生成和处理，这通常被视为后续传统计算的准备步骤，因为快速方法具有交互性，其近似性质。1994 年，布鲁克斯及其同事引入了 Sculpt，这是一个用于处理小蛋白质的建模系统，它通过连续能量最小化来实现。Sculpt 限制了键长和键角，但连续最小化了由于扭转角、氢键、范德华力和静电相互作用而产生的势能。Sculpt 允许操作员使用计算机鼠标操纵蛋白质，并且对于一个 20 个残基的蛋白质，可以达到 11 Hz 的更新率。为了简化大分子结构的设置，分子编辑器允许使用经典力场或非常近似的非迭代半经验方法进行快速（实时）结构优化，如 Avogadro (223) 和 SAMSON (224,225) 所实现。 在 SAMSON 环境中，Redon 及其同事应用自适应动力学来实现对更大蛋白质和碳氢化合物的交互式建模(226)。他们还依靠连续能量最小化，并允许对分子结构（原子添加和删除）进行操作，而不仅仅是其操纵(227)。他们认识到非反应力场的局限性，并研究了半经验量子化学方法(225,228)的应用，并将通用力场扩展以支持分子拓扑的变化(229)。
不同方法出现，以允许在虚拟环境中可视化分子结构或分子动力学模拟，有时还具备编辑和操纵分子的功能。 Harvey 和 Gingold 于 2000 年使用触觉设备探索了原子轨道的电子密度。 Comai 和 Mazza 开发了一种类似工具，用于感知量子化学计算产生的静电场。 Satoh 等人设计了一个框架，用于研究由经典力场描述的稀有气体范德华相互作用，并具有触觉反馈。 触觉设备后来被用于蛋白质溶剂可及表面的交互式探索。 不同的研究证明了沉浸式和交互式方法在教育中的潜在益处，并为多人同时沉浸设计了多个虚拟现实框架，允许协作环境。
4.2. 量子力学计算的交互性
传统上，量子化学研究因成本过高而无法实现交互性。这是由于量子力学方程的数学结构，其中涉及大量积分的昂贵计算和迭代求解过程（与从经典力场导出的能量和力的解析公式的直接快速评估形成对比）。因此，长期以来，量子力学方法一直被认为不适合交互式方法（然而，请参见下一节）。
为了确定电子能和其他性质，量子化学计算需要，如同所有计算建模方法，三个步骤，如图图2所示：设置、计算和结果分析。对于设置，通常创建一个包含计算设置和分子系统规范的基于文本的输入文件。计算步骤通常在中央处理器（CPUs）或其核心上执行。量子化学计算通常需要几分钟到几周的计算时间。然后，为了分析结果，从生成的输出文件中解析感兴趣的值。对于计算量子化学的从业者来说，众所周知，计算时间是耗时最长的步骤。鉴于实际计算所需的努力，设置和分析时间显得微不足道。
图 2
图 2. 典型量子化学计算的示意图。（a）传统上，最耗时的步骤是在 CPU 上的计算步骤。（b）随着 CPU 性能的提高，对于固定系统大小和某些给定的电子结构模型，量子化学计算的时间会减少。（c）对于准瞬时计算，最耗时的步骤现在不再是计算本身，而是瓶颈变成了设置和分析结果。
摩尔定律通常被观察到的说法是，芯片上的晶体管数量大约每两年翻一番。对于量子化学来说，这种发展非常有益（并且由于 CPU 核心数量的增加以及所有量子化学软件现在固有的并行性，这种发展还没有结束）。一方面，它使得可以以更高的精度研究更大的分子系统。另一方面，如果研究系统的大小或算法的精度没有增加，那么随着更高效的硬件的可用性，计算时间将逐年减少，如图 2b 所示。随着 CPU 功率的持续增加，计算时间可以大大减少，直到计算几乎瞬间完成。在这种情况下，传统方法（设置、计算、分析）由设置和分析主导，而不是计算本身，如图 2c 所示。此外，对于几乎瞬间的计算，设置和分析在时间上不再分离。
在传统方法中，设置和分析步骤并未从日益增长的计算能力中受益。虽然对于耗时计算，设置和分析所需的时间和人力与计算本身相比微不足道，但对于几乎瞬间的计算来说并非如此。要充分利用几乎瞬间的计算，必须完全摒弃传统意义上的基于文本的设置和分析，并考虑完全交互式的方法来研究反应性。请注意，即使是大多数高级分子编辑器也无法缓解这个问题，因为它们在设置输入和检查结果方面提供帮助，但总的来说，并没有达到这种程度：（i）几乎是瞬间的，并且（ii）能够应对不断操纵的分子结构产生的新结果的无尽数据流入。相比之下，真正的量子力学计算交互性开辟了新的研究领域，这些领域结合了计算机和人类技能的优势，使我们能够在分子反应性（与硬编码的经典力场形成对比）方面做出无偏见的发现，正如我们现在将要讨论的。
在考虑化学反应活性研究时，我们注意到这自然需要基于基本粒子的物理建模，从而基于量子力学。只有电子和原子核的已知电磁相互作用算子才能使我们量化在化学反应空间探索研究中遇到的分子系统任意配置中原子和片段的涌现相互作用能量。研究化学反应活性的首次交互式方法出现在过去十年中。它们考虑了基于量子力学第一原理的 PES 的交互式探索，以确定反应机理，因此需要应用量子化学方法。在 2009 年，我们提出了触觉量子化学（HQC）作为探索使用触觉设备（其中力起描述斜率的作用，并在一定程度上也描述曲率）的势能面的框架。《a id=0》（250）触觉力反馈最初依赖于从预先计算的ab initio电子能数据点在构型空间中开始的插值方案。 HQC 的底层算法后来得到了改进和扩展，以实现更自动化和灵活的工作流程。此后，我们的原始 HQC 实现被修改，不再依赖于插值，而是基于实时单点计算。这种新方法需要一个实时量子化学（RTQC）框架，该框架在密度泛函理论模型中的小分子系统或半经验模型中包含约 100 个原子的系统中已被证明是可行的。在 SAMSON 分子编辑器中实现了这一方法，并展示了 RTQC 的应用性和实用性。RTQC 框架的主要组件如图 3 所示。
图 3
图 3. 实时量子化学框架的主要组件。中心元素是正在研究的分子结构（中央），显示在操作员面前（右上角）。操作员可以使用鼠标或触觉设备移动原子，并体验其操作的效果（左上角）。单点计算在后台持续运行（底部），提供反应性探索背后的核力以及其他相关量子化学性质。
量子化学计算交互性的主要问题是单点能量计算需要自洽场（SCF）迭代。这个迭代过程在标准量子化学计算中已经存在一些困难，但在交互式方法中尤其麻烦。首先，无法预先预测单点计算需要多少时间，尤其是对于操作者引入的快速和剧烈的结构修改。由于执行时间与 SCF 迭代次数相关，这强烈激励着减少这个数量，这可以通过改善 SCF 周期的初始电子密度来实现。其次，可能会出现 SCF 过程根本不收敛或需要大量迭代的情况。不收敛的计算会导致交互式模拟中传递的属性流中断，从而破坏对虚拟分子世界的沉浸感。第三，SCF 方程可能有不同的解，导致不同的电子密度和量子化学性质。 在交互式环境中，收敛到错误的 SCF 解可能会导致对所研究分子系统的描述存在偏差。
在过去的几年里，我们开发了针对所有这些问题的方法，最终使我们能够在交互式量子力学环境中应用基于 SCF 的电子结构方法来探索反应机理。重要的是要理解，我们将在本节剩余部分讨论的所有这些发展，都解决了两个挑战：(i)效率，导致计算更快；(ii)稳定性，确保可靠的结果。而这两个挑战在交互式环境中都需要令人信服的解决方案，因为在 100 毫秒到 1 秒的速率下提供大量结果（简单地说，根本不允许检查可能存在错误的结果，因此必须不惜一切代价避免或纠正它们），我们强调，它们对于上述第 1 类和第 2 类中讨论的自动化黑盒算法也很重要，在这些算法中，由于产生的数据量巨大，手动检查可靠性变得不可能（因此计算不能失败）。
为解决第一个问题，我们通过密度传播算法加速了（相似）结构的自洽场计算。(255)这种策略与应用于从头算分子动力学中的其他外推方法相关。(256,257)它为单点计算提供了改进的初始密度矩阵，从而减少了收敛所需的迭代次数。
考虑到第二个挑战，在计算缓慢或根本不收敛的情况下，视觉和触觉反馈也必须是强制性的。为了保证可靠的实时反馈，我们引入了一种中介策略。中介创建近似势能表面的代理势，并实现高频反馈。此外，中介限制了反应性探索到配置空间中可用轨道可靠的区域，直到新数据最终可用。
至于第三个困难，不正确的收敛计算往往在非交互反应性研究中被忽视或未被检测到。为确保交互式探索依赖于正确的收敛量子化学计算，我们提出了一种可以快速评估的方案（在 RTQC 框架中所需），并且通过随机混合扰动轨道，以便检测并纠正不正确的自洽场收敛。(259) 该方案持续在后台测试，是否可以通过随机扰动的初始电子密度获得更低能量的解。
除了使反应性研究更加直观外，交互式量子化学还推动了量子化学研究方法的新途径。最重要的是，探索不必局限于具有固定电荷和自旋状态的特定、预定义的势能面。由于量子化学计算速度快，可以在后台自动计算其他状态和性质，以便在探索的结构中通知操作员，否则可能会错过关于反应性的重要事实。为此，我们引入了分子倾向的概念，通过该概念可以同时探索分子系统的多个状态。《(260)》这为化学家提供了发现反应系统发生（意外）转化（如还原、氧化、自旋交叉、光激发或质子化）倾向的可能性。
为了交互式地探索反应性，必须跟踪在交互式探索中看到的结构和反应。为此，必须处理原始探索数据，以确定稳定的分子结构以及将它们连接起来的反应网络。这可以通过将探索过程中记录的结构序列转换为 B 样条曲线来实现，从中我们提取稳定结构和基本反应的候选者。然后对这些候选者进行优化并存储在反应网络中。请注意，这个结构网络可以与第 1 类和第 2 类的算法相同的数据库，因此以综合的方式促进所有类别的协同作用。为了以自动化的方式完成反应途径和过渡状态的稳定优化，我们开发了一种新的两端方法，称为 ReaDuct，该方法通过参数化曲线描述反应途径。为了确定最低能量途径和过渡状态，它优化曲线的参数，而不是反应路径上的离散结构。
5. 结论与展望
点击复制章节链接Section link copied!
在这项工作中，我们回顾了为有效和高效探索复杂化学反应而开发的不同方法。虽然利用 PES 上局部曲率信息的方法非常系统，但它们可能受到计算成本的限制，并且很难将这种探索引导到 PES 中真正相关的区域（对于给定的反应物和反应条件）。相比之下，利用某种启发式方法的方法可能通过采用基于图变换规则或量子力学概念来加速探索，从而发现潜在的中间体。因此，跨越 PES 的探索变得可行。当启发式方法基于从电子波函数中直接提取的信息时，这些启发式方法可以制定得适用于包含整个元素周期表中分子的系统。
交互式方法使用户能够通过配置空间引导感兴趣的系统，从而有效地探索用户认为与所考虑的化学系统相关的特定区域。然而，由于这种探索不是系统的，关键的反应途径可能仍未被发现。为了实现交互性和沉浸到分子世界，需要超快速的单点计算。虽然原则上可以使用密度泛函理论（DFT）的方法进行此类计算，(221,252)但迄今为止，实时量子化学框架仍然依赖于半经验方法，(253)这些方法在 1 类和 2 类的算法中也具有优势，并在实际应用中占有一席之地（然而，请记住我们在第 2 类部分对可靠性和误差估计的评论）。
我们强调，在 1-3 类中，没有任何方法能保证在探索过程中找到某些反应网络的所有重要基本步骤。然而，它们都比繁琐且有限的手动检查要好得多，提供了比后者更多的细节。在彻底性和计算可处理性之间取得平衡仍然是一个挑战。在图 4 中，不同类别的优势总结在了一个维恩图中。通过结合所有三个类别的优势，可以制定出一个真正可靠且普遍适用的探索方案。在我们的实验室中，目前正在开发一个名为 SCINE 的软件包（262），其中这三个方法完全互操作。
图 4
图 4. 三种探索策略的联合优势产生了一种普遍适用的探索协议。
作者信息
点击复制章节链接Section link copied!
马克斯·雷耶尔 - 瑞士苏黎世联邦理工学院物理化学实验室，弗拉基米尔-普雷洛格街 2 号，8093 苏黎世，瑞士
https://orcid.org/0000-0002-9508-1565;
传记
点击复制章节链接Section link copied!
Gregor N. Simm
格奥尔格·N·西姆出生于德国埃尔兰根，并在那里长大。他在苏黎世联邦理工学院（ETH Zurich）完成了学士和硕士学位，主修跨学科科学。2014 年，他在哈佛大学阿兰·阿斯普鲁-古齐克教授的指导下完成了硕士学位论文，研究机器学习技术以加速新有机光伏材料的发现。从 2015 年到 2018 年，他在德国化学工业基金会资助下，在马克斯·赖尔教授的指导下担任博士研究生。他开发了具有误差估计能力的复杂化学反应网络探索方法。自 2018 年秋季以来，他一直在剑桥大学机器学习小组担任博士后研究员，由瑞士国家科学基金会提供的早期博士后流动奖学金支持。
Alain C. Vaucher
艾兰·C·瓦彻于 1990 年出生于瑞士。在苏黎世联邦理工学院获得化学学士和硕士学位后，他成为马克斯·赖尔教授团队的一名博士研究生，在那里他的研究集中在量子化学的交互式方法上。他的博士论文获得了 2018 年 IBM 研究奖。在苏黎世联邦理工学院期间，他对科学计算和新技术产生了浓厚的兴趣。他目前的研究致力于化学中人工智能的应用。
Markus Reiher
马克斯·雷耶尔于 1971 年出生于东西菲利亚。他在 1998 年从比勒费尔德大学获得理论化学博士学位，与于尔根·欣泽合作，并在埃尔兰根、波恩和耶拿大学担任讲师和教授。自 2006 年以来，他一直担任苏黎世联邦理工学院的理论化学教授。他的研究集中在相对论量子化学、理论光谱学、电子相关方法、密度泛函理论、反应机理、不确定性量化、交互式量子力学、配位化学和量子计算。
致谢
点击复制章节链接Section link copied!
这项工作得到了瑞士国家基金会的财务支持。
参考文献
点击复制章节链接Section link copied!
本文引用
262 篇其他出版物。
1Masters, C. 均相过渡金属催化：一门温柔的艺术，第 1 版；Springer，2011 年。
强化2，R. Vinu；L. J. Broadbelt. 解开复杂系统的反应途径并指定反应动力学。化学与生物分子工程年度评论 2012，3，29–54，DOI： 10.1146/annurev-chembioeng-062011-081108- 3Ross, J. Determination of Complex Reaction Mechanisms. Analysis of Chemical, Biological and Genetic Networks. J. Phys. Chem. A 2008, 112, 2134– 2143, DOI: 10.1021/jp711313e
- 4Jorgensen, W. L. The Many Roles of Computation in Drug Discovery. Science 2004, 303, 1813– 1818, DOI: 10.1126/science.1096361Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXitFehu7w%253D&md5=77b2fac63e750ca7cdc7e4f35654549aThe Many Roles of Computation in Drug DiscoveryJorgensen, William L.Science (Washington, DC, United States) (2004), 303 (5665), 1813-1818CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review. An overview is given on the diverse uses of computational chem. in drug discovery. Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for detg. protein-ligand binding.
- 5Valdez, C. E.; Morgenstern, A.; Eberhart, M. E.; Alexandrova, A. N. Predictive Methods for Computational Metalloenzyme Redesign – a Test Case with Carboxypeptidase A. Phys. Chem. Chem. Phys. 2016, 18, 31744– 31756, DOI: 10.1039/C6CP02247BGoogle Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFCrsbbO&md5=b11bfcb0cc2fec4149ad6f9fc28ffa66Predictive methods for computational metalloenzyme redesign - a test case with carboxypeptidase AValdez, Crystal E.; Morgenstern, Amanda; Eberhart, Mark E.; Alexandrova, Anastassia N.Physical Chemistry Chemical Physics (2016), 18 (46), 31744-31756CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Computational metalloenzyme design is a multi-scale problem. It requires treating the metal coordination quantum mech., extensive sampling of the protein backbone, and addnl. accounting for the polarization of the active site by both the metal cation and the surrounding protein (a phenomenon called electrostatic preorganization). We bring together a combination of theor. methods that jointly offer these desired qualities: QM/DMD for mixed quantum-classical dynamic sampling, quantum theory of atoms in mols. (QTAIM) for the assessment of electrostatic preorganization, and D. Functional Theory (DFT) for mechanistic studies. Within this suite of principally different methods, there are both complementarity of capabilities and cross-validation. Using these methods, predictions can be made regarding the relative activities of related enzymes, as we show on the native Zn2+-dependent carboxypeptidase A (CPA), and its mutant proteins, which are hypothesized to hydrolyze modified substrates. For the native CPA, we replicated the catalytic mechanism and the rate in close agreement with the expt., giving validity to the QM/DMD predicted structure, the DFT mechanism, and the QTAIM assessment of catalytic activity. For most sequences of the modified substrate and tried CPA mutants, substantially worsened activity is predicted. However, for the substrate mutant that contains Asp instead of Phe at the C-terminus, one CPA mutant exhibits a reasonable activity, as predicted across the theor. methods. CPA is a well-studied system, and here it serves as a testing ground for the offered methods.
- 6Honkala, K.; Hellman, A.; Remediakis, I. N.; Logadottir, A.; Carlsson, A.; Dahl, S.; Christensen, C. H.; Nørskov, J. K. Ammonia Synthesis from First-Principles Calculations. Science 2005, 307, 555– 558Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslOjuw%253D%253D&md5=4c6066f84d200c9c587b6dd1dcd3b0bfAmmonia Synthesis from First-Principles CalculationsHonkala, K.; Hellman, A.; Remediakis, I. N.; Logadottir, A.; Carlsson, A.; Dahl, S.; Christensen, C. H.; Norskov, J. K.Science (Washington, DC, United States) (2005), 307 (5709), 555-558CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The rate of ammonia synthesis over a nanoparticle ruthenium catalyst can be calcd. directly on the basis of a quantum chem. treatment of the problem using d. functional theory. We compared the results to measured rates over a ruthenium catalyst supported on magnesium aluminum spinel. When the size distribution of ruthenium particles measured by transmission electron microscopy was used as the link between the catalyst material and the theor. treatment, the calcd. rate was within a factor of 3 to 20 of the exptl. rate. This offers hope for computer-based methods in the search for catalysts.
- 7Medford, A. J.; Wellendorff, J.; Vojvodic, A.; Studt, F.; Abild-Pedersen, F.; Jacobsen, K. W.; Bligaard, T.; Nørskov, J. K. Assessing the Reliability of Calculated Catalytic Ammonia Synthesis Rates. Science 2014, 345, 197– 200, DOI: 10.1126/science.1253486Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFWjtLvK&md5=af3416666eeec422dd8f7c7543b9488eAssessing the reliability of calculated catalytic ammonia synthesis ratesMedford, Andrew J.; Wellendorff, Jess; Vojvodic, Aleksandra; Studt, Felix; Abild-Pedersen, Frank; Jacobsen, Karsten W.; Bligaard, Thomas; Norskov, Jens K.Science (Washington, DC, United States) (2014), 345 (6193), 197-200CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)We introduce a general method for estg. the uncertainty in calcd. materials properties based on d. functional theory calcns. We illustrate the approach for a calcn. of the catalytic rate of ammonia synthesis over a range of transition-metal catalysts. The correlation between errors in d. functional theory calcns. is shown to play an important role in reducing the predicted error on calcd. rates. Uncertainties depend strongly on reaction conditions and catalyst material, and the relative rates between different catalysts are considerably better described than the abs. rates. We introduce an approach for incorporating uncertainty when searching for improved catalysts by evaluating the probability that a given catalyst is better than a known std.
- 8Matera, S.; Maestri, M.; Cuoci, A.; Reuter, K. Predictive-Quality Surface Reaction Chemistry in Real Reactor Models: Integrating First-Principles Kinetic Monte Carlo Simulations into Computational Fluid Dynamics. ACS Catal. 2014, 4, 4081– 4092, DOI: 10.1021/cs501154eGoogle Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs12kurjF&md5=e0f052a4546ccf857b9e898b8d08825bPredictive-Quality Surface Reaction Chemistry in Real Reactor Models: Integrating First-Principles Kinetic Monte Carlo Simulations into Computational Fluid DynamicsMatera, Sebastian; Maestri, Matteo; Cuoci, Alberto; Reuter, KarstenACS Catalysis (2014), 4 (11), 4081-4092CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)We present a numerical framework to integrate first-principles kinetic Monte Carlo (1p-kMC) based microkinetic models into the powerful computational fluid dynamics (CFD) package CatalyticFoam. This allows for the simultaneous account of a predictive-quality surface reaction kinetics inside an explicitly described catalytic reactor geometry. Crucial means toward an efficient and stable implementation are the exploitation of the disparate time scales of surface chem. and gas-phase transport, as well as the reliable interpolation of irregularly gridded 1p-kMC data by means of an error-based modified Shepard approach. We illustrate the capabilities of the framework using the CO oxidn. at Pd(100) and RuO2(110) model catalysts in different reactor configurations and fluid dynamic conditions as showcases. These showcases underscore both the necessity and value of having reliable treatments of the surface chem. and flow inside integrated multiscale catalysis simulations when aiming at an at.-scale understanding of the catalytic function in near-ambient environments. Our examples highlight how intricately this function is affected by specifics of the reactor geometry and heat dissipation channels on the one end, and on the other end by characteristics of the intrinsic catalytic activity that are only captured by treatments beyond prevalent mean-field rate equations.
- 9Reuter, K. Ab Initio Thermodynamics and First-Principles Microkinetics for Surface Catalysis. Catal. Lett. 2016, 146, 541– 563, DOI: 10.1007/s10562-015-1684-3Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xps1CnsQ%253D%253D&md5=352bd644b8fabaf14fc7e70d0f29b5a0Ab Initio Thermodynamics and First-Principles Microkinetics for Surface CatalysisReuter, KarstenCatalysis Letters (2016), 146 (3), 541-563CODEN: CALEER; ISSN:1011-372X. (Springer)A review; ab initio thermodn. and first-principles microkinetic simulations have become std. tools in research on model catalysts. Complementing dedicated in situ expts. these techniques contribute to our evolving mechanistic understanding, in particular of a reaction-induced dynamical evolution of the working catalyst surface. This topical review surveys the methodol. foundations and ongoing developments of both techniques, and specifically illustrates the type of insights they provide in the context of in situ model catalyst studies. This insight points at substantial deviations from the std. picture that analyzes catalytic function merely in terms of properties of and processes at active sites as they emerge from a crystal lattice truncation of the nominal catalyst bulk material.
- 10Baxter, E. T.; Ha, M.-A.; Cass, A. C.; Alexandrova, A. N.; Anderson, S. L. Ethylene Dehydrogenation on Pt4,7,8 Clusters on Al2O3: Strong Cluster Size Dependence Linked to Preferred Catalyst Morphologies. ACS Catal. 2017, 7, 3322– 3335, DOI: 10.1021/acscatal.7b00409Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltVSqsbc%253D&md5=d1944c4c7de19d6e44ea69ac739c458dEthylene Dehydrogenation on Pt4,7,8 Clusters on Al2O3: Strong Cluster Size Dependence Linked to Preferred Catalyst MorphologiesBaxter, Eric T.; Ha, Mai-Anh; Cass, Ashley C.; Alexandrova, Anastassia N.; Anderson, Scott L.ACS Catalysis (2017), 7 (5), 3322-3335CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Catalytic dehydrogenation of ethylene on size-selected Ptn (n = 4, 7, 8) clusters deposited on the surface of Al2O3 was studied exptl. and theor. Clusters were mass-selected, deposited on the alumina support, and probed by a combination of low energy ion scattering, temp.-programmed desorption and reaction of C2D4 and D2, XPS, d. functional theory, and statistical mech. theory. Pt7 is identified as the most catalytically active cluster, while Pt4 and Pt8 exhibit comparable activities. The higher activity can be related to the cluster structure and particularly to the distribution of cluster morphologies accessible at the temps. and coverage with ethylene in catalytic conditions. Specifically, while Pt7 and Pt8 on alumina have very similar prismatic global min. geometries, Pt7 at higher temps. also has access to single-layer isomers, which become more and more predominant in the cluster catalyst ensemble upon increasing ethylene coverage. Single-layer isomers feature greater charge transfer from the support and more binding sites that activate ethylene for dehydrogenation rather than hydrogenation or desorption. Size-dependent susceptibility to coking and deactivation was also studied. Results show that size-dependent catalytic activity of clusters is not a simple property of single cluster geometry but the av. over a statistical ensemble at relevant conditions.
- 11Ha, M.-A.; Baxter, E. T.; Cass, A. C.; Anderson, S. L.; Alexandrova, A. N. Boron Switch for Selectivity of Catalytic Dehydrogenation on Size-Selected Pt Clusters on Al2O3. J. Am. Chem. Soc. 2017, 139, 11568– 11575, DOI: 10.1021/jacs.7b05894Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1GjsbrO&md5=c4fb4ca3671fed66af60f96ac51a86cbBoron Switch for Selectivity of Catalytic Dehydrogenation on Size-Selected Pt Clusters on Al2O3Ha, Mai-Anh; Baxter, Eric T.; Cass, Ashley C.; Anderson, Scott L.; Alexandrova, Anastassia N.Journal of the American Chemical Society (2017), 139 (33), 11568-11575CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Size-selected supported clusters of transition metals can be remarkable and highly tunable catalysts. A particular example is Pt clusters deposited on alumina, which have been shown to dehydrogenate hydrocarbons in a size-specific manner. Pt7, of the three sizes studied, is the most active and, therefore, like many other catalysts, deactivates by coking during reactions in hydrocarbon-rich environments. Using a combination of expt. and theory, we show that nanoalloying Pt7 with boron modifies the alkene-binding affinity to reduce coking. From a fundamental perspective, the comparison of exptl. and theor. results shows the importance of considering not simply the most stable cluster isomer, but rather the ensemble of accessible structures as it changes in response to temp. and reagent coverage.
- 12Ulissi, Z. W.; Medford, A. J.; Bligaard, T.; Nørskov, J. K. To Address Surface Reaction Network Complexity Using Scaling Relations Machine Learning and DFT Calculations. Nat. Commun. 2017, 8, 14621, DOI: 10.1038/ncomms14621Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czjtFamuw%253D%253D&md5=bde19b4dcb6abce90b2ea7ab073e1c6eTo address surface reaction network complexity using scaling relations machine learning and DFT calculationsUlissi Zachary W; Norskov Jens K; Medford Andrew J; Bligaard ThomasNature communications (2017), 8 (), 14621 ISSN:.Surface reaction networks involving hydrocarbons exhibit enormous complexity with thousands of species and reactions for all but the very simplest of chemistries. We present a framework for optimization under uncertainty for heterogeneous catalysis reaction networks using surrogate models that are trained on the fly. The surrogate model is constructed by teaching a Gaussian process adsorption energies based on group additivity fingerprints, combined with transition-state scaling relations and a simple classifier for determining the rate-limiting step. The surrogate model is iteratively used to predict the most important reaction step to be calculated explicitly with computationally demanding electronic structure theory. Applying these methods to the reaction of syngas on rhodium(111), we identify the most likely reaction mechanism. Propagating uncertainty throughout this process yields the likelihood that the final mechanism is complete given measurements on only a subset of the entire network and uncertainty in the underlying density functional theory calculations.
- 13Vereecken, L.; Glowacki, D. R.; Pilling, M. J. Theoretical Chemical Kinetics in Tropospheric Chemistry: Methodologies and Applications. Chem. Rev. 2015, 115, 4063– 4114, DOI: 10.1021/cr500488pGoogle Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXmtVWqs7s%253D&md5=75c3bde1b210e3c1555d0c946f8e4976Theoretical Chemical Kinetics in Tropospheric Chemistry: Methodologies and ApplicationsVereecken, Luc; Glowacki, David R.; Pilling, Michael J.Chemical Reviews (Washington, DC, United States) (2015), 115 (10), 4063-4114CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review is presented. Chem. Kinetics in Tropospheric Chem. is studied.
- 14Ludlow, R. F.; Otto, S. Systems Chemistry. Chem. Soc. Rev. 2008, 37, 101– 108, DOI: 10.1039/B611921MGoogle Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtVWhtQ%253D%253D&md5=151c83f30396538fccc0ea2f9c016d26Systems chemistryLudlow, R. Frederick; Otto, SijbrenChemical Society Reviews (2008), 37 (1), 101-108CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A tutorial review. The study of complex mixts. of interacting synthetic mols. has historically not received much attention from chemists, even though research into complexity is well established in the neighboring fields. However, with the huge recent interest in systems biol. and the availability of modern anal. techniques this situation is likely to change. In this tutorial review we discuss some of the incentives for developing systems chem. and we highlight the pioneering work in which mol. networks are making a splash. A distinction is made between networks under thermodn. and kinetic control. The former include dynamic combinatorial libraries while the latter involve pseudo-dynamic combinatorial libraries, oscillating reactions and networks of autocatalytic and replicating compds. These studies provide fundamental insights into the organizational principles of mol. networks and how these give rise to emergent properties such as amplification and feedback loops, and may eventually shed light on the origin of life. The knowledge obtained from the study of mol. networks should ultimately enable us to engineer new systems with properties and functions unlike any conventional materials.
- 15Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic Chemistry; Oxford University Press: Oxford, 2001.Google ScholarThere is no corresponding record for this reference.
- 16Dewyer, A. L.; Argüelles, A. J.; Zimmerman, P. M. Methods for Exploring Reaction Space in Molecular Systems. WIREs Comput. Mol. Sci. 2018, 8, e1354 DOI: 10.1002/wcms.1354
- 17Sameera, W. M. C.; Maeda, S.; Morokuma, K. Computational Catalysis Using the Artificial Force Induced Reaction Method. Acc. Chem. Res. 2016, 49, 763– 773, DOI: 10.1021/acs.accounts.6b00023Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvFSnsb0%253D&md5=761857a94f5b7c7366b98650d8a42646Computational Catalysis Using the Artificial Force Induced Reaction MethodSameera, W. M. C.; Maeda, Satoshi; Morokuma, KeijiAccounts of Chemical Research (2016), 49 (4), 763-773CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)The artificial force induced reaction (AFIR) method in the global reaction route mapping (GRRM) strategy is an automatic approach to explore all important reaction paths of complex reactions. Most traditional methods in computational catalysis require guess reaction paths. On the other hand, the AFIR approach locates local min. (LMs) and transition states (TSs) of reaction paths without a guess, and therefore finds unanticipated as well as anticipated reaction paths. The AFIR method has been applied for multicomponent org. reactions, such as the aldol reaction, Passerini reaction, Biginelli reaction, and phase-transfer catalysis. In the presence of several reactants, many equil. structures are possible, leading to a no. of reaction pathways. The AFIR method in the GRRM strategy dets. all of the important equil. structures and subsequent reaction paths systematically. As the AFIR search is fully automatic, exhaustive trial-and-error and guess-and-check processes by the user can be eliminated. At the same time, the AFIR search is systematic, and therefore a more accurate and comprehensive description of the reaction mechanism can be detd.The AFIR method has been used for the study of full catalytic cycles and reaction steps in transition metal catalysis, such as cobalt-catalyzed hydroformylation and iron-catalyzed carbon-carbon bond formation reactions in aq. media. Some AFIR applications have targeted the selectivity-detg. step of transition-metal-catalyzed asym. reactions, including stereoselective water-tolerant lanthanide Lewis acid-catalyzed Mukaiyama aldol reactions. In terms of establishing the selectivity of a reaction, systematic sampling of the transition states is crit. In this direction, AFIR is very useful for performing a systematic and automatic detn. of TSs. In the presence of a comprehensive description of the transition states, the selectivity of the reaction can be calcd. more accurately.For relatively large mol. systems, the computational cost of AFIR searches can be reduced by using the ONIOM(QM:QM) or ONIOM(QM:MM) methods. In common practice, d. functional theory (DFT) with a relatively small basis set is used for the high-level calcn., while a semiempirical approach or a force field description is used for the low-level calcn. After approx. LMs and TSs are detd., std. computational methods (e.g., DFT with a large basis set) are used for the full mol. system to det. the true LMs and TSs and to rationalize the reaction mechanism and selectivity of the catalytic reaction.The examples in this Account evidence that the AFIR method is a powerful approach for accurate prediction of the reaction mechanisms and selectivities of complex catalytic reactions. Therefore, the AFIR approach in the GRRM strategy is very useful for computational catalysis.
- 18Hawkins, P. C. D. Conformation Generation: The State of the Art. J. Chem. Inf. Model. 2017, 57, 1747– 1756, DOI: 10.1021/acs.jcim.7b00221Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFagu7bE&md5=776818e66798d1987e015440a28e208eConformation Generation: The State of the ArtHawkins, Paul C. D.Journal of Chemical Information and Modeling (2017), 57 (8), 1747-1756CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The generation of conformations for small mols. is a problem of continuing interest in cheminformatics and computational drug discovery. This review will present an overview of methods used to sample conformational space, focusing on those methods designed for org. mols. commonly of interest in drug discovery. Different approaches to both the sampling of conformational space and the scoring of conformational stability will be compared and contrasted, with an emphasis on those methods suitable for conformer sampling of large nos. of drug-like mols. Particular attention will be devoted to the appropriate utilization of information from exptl. solid-state structures in validating and evaluating the performance of these tools. The review will conclude with some areas worthy of further investigation.
- 19Ohno, K.; Maeda, S. A Scaled Hypersphere Search Method for the Topography of Reaction Pathways on the Potential Energy Surface. Chem. Phys. Lett. 2004, 384, 277– 282, DOI: 10.1016/j.cplett.2003.12.030Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXksFWguw%253D%253D&md5=d695800fcf7c758ae9e5f6213d187edaA scaled hypersphere search method for the topography of reaction pathways on the potential energy surfaceOhno, Koichi; Maeda, SatoshiChemical Physics Letters (2004), 384 (4-6), 277-282CODEN: CHPLBC; ISSN:0009-2614. (Elsevier Science B.V.)An algorithm for finding pathways to transition states (TS) or dissocn. channels (DC) from equil. structures (EQ) on the potential energy surface (PES) is presented. The pathways around an EQ can be discovered at min. on the scaled hypersphere which would have a const. energy when the potentials are harmonic. Topog. maps including all TS, DC, and EQ were obtained for ab initio PES of H2O and HCHO in the MP2/3-21G level. The present scaled hypersphere search technique in combination with a downhill-walk algorithm enables us to make a topog. anal. of the PES for a given chem. compn.
- 20Maeda, S.; Ohno, K. Ab Initio Studies on Synthetic Routes of Glycine from Simple Molecules via Ammonolysis of Acetolactone: Applications of the Scaled Hypersphere Search Method. Chem. Lett. 2004, 33, 1372– 1373, DOI: 10.1246/cl.2004.1372
- 21Maeda, S.; Ohno, K. Global Mapping of Equilibrium and Transition Structures on Potential Energy Surfaces by the Scaled Hypersphere Search Method: Applications to Ab Initio Surfaces of Formaldehyde and Propyne Molecules. J. Phys. Chem. A 2005, 109, 5742– 5753, DOI: 10.1021/jp0513162Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXksl2mtLk%253D&md5=68d94d344ec0774f5313ba93e456ffe3Global Mapping of Equilibrium and Transition Structures on Potential Energy Surfaces by the Scaled Hypersphere Search Method: Applications to ab Initio Surfaces of Formaldehyde and Propyne MoleculesMaeda, Satoshi; Ohno, KoichiJournal of Physical Chemistry A (2005), 109 (25), 5742-5753CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Tech. details of a new global mapping technique for finding equil. (EQ) and transition structures (TS) on potential energy surfaces (PES), the scaled hypersphere search (SHS) method (Ohno, K.; Maeda, S. Chem. Phys. Lett. 2004, 384, 277), are presented. On the basis of a simple principle that reaction pathways are found as anharmonic downward distortions of PES around an EQ point, the reaction pathways can be obtained as energy min. on the scaled hypersphere surface, which would have a const. energy when the potentials are harmonic. Connections of SHS paths between each EQ are very similar to corresponding intrinsic reaction coordinate (IRC) connections. The energy max. along the SHS path reaches a region in close proximity to the TS of the reaction pathway, and the subsequent geometry optimization from the SHS max. structure easily converges to the TS. The SHS method, using the one-after-another algorithm connecting EQ and TS, considerably reduces the multidimensional space to be searched to certain limited regions around the pathways connecting each EQ with the neighboring TS. Applications of the SHS method have been made to ab initio surfaces of formaldehyde and propyne mols. to obtain systematically five EQ and nine TS for formaldehyde and seven EQ and 32 TS for propyne.
- 22Ohno, K.; Maeda, S. Global Reaction Route Mapping on Potential Energy Surfaces of Formaldehyde, Formic Acid, and Their Metal-Substituted Analogues. J. Phys. Chem. A 2006, 110, 8933– 8941, DOI: 10.1021/jp061149lGoogle Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XlvVWlsLk%253D&md5=b057c5984bdd877c2a57f80cfe6aa8a6Global Reaction Route Mapping on Potential Energy Surfaces of Formaldehyde, Formic Acid, and Their Metal-Substituted AnaloguesOhno, Koichi; Maeda, SatoshiJournal of Physical Chemistry A (2006), 110 (28), 8933-8941CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Global reaction route mapping of equil. structures, transition structures, and their connections on potential energy surface (PES) has been done for MCHO (M = H, Li, Na, Al, Cu) and HCO2M (M = H, Li). A one-after-another technique based on the scaled hypersphere search method has been successfully applied to exploring unknown chem. structures, transition structures, and reaction pathways for organometallic systems. Upon metal substitution, considerable changes of stable structures, reaction pathways, and relative heights of transition structures have been discovered, though some features are similar among the analogs. Al and Cu atoms were found to behave as very strong scissors to cut the CO double bond in MCHO. Energy profiles of the CO insertion into Li-H and Li-CH3 bonds were found to be very similar, esp. around the structures where the Li atom is not directly connected with the Me group, which indicates little effects of alkyl substitution on the reaction route topol.
- 23Maeda, S.; Ohno, K.; Morokuma, K. Systematic Exploration of the Mechanism of Chemical Reactions: The Global Reaction Route Mapping (GRRM) Strategy Using the ADDF and AFIR Methods. Phys. Chem. Chem. Phys. 2013, 15, 3683– 3701, DOI: 10.1039/c3cp44063jGoogle Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXislynsrg%253D&md5=3091bebd5edabab18bdabe51eb001e65Systematic exploration of the mechanism of chemical reactions: the global reaction route mapping (GRRM) strategy using the ADDF and AFIR methodsMaeda, Satoshi; Ohno, Koichi; Morokuma, KeijiPhysical Chemistry Chemical Physics (2013), 15 (11), 3683-3701CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Global reaction route mapping (GRRM), a fully-automated search for all important reaction pathways relevant to a given purpose, from quantum chem. calcns. enables systematic elucidation of complex chem. reaction mechanisms. However, GRRM had previously been limited to very simple systems. This is mainly because such calcns. are highly demanding even in small systems when a brute-force sampling is considered. Hence, the authors have developed two independent but complementary methods: anharmonic downward distortion following (ADDF) and artificial force induced reaction (AFIR) methods. ADDF can follow reaction pathways starting from local min. on the potential energy surface (PES) toward transition structures (TSs) and dissocn. channels. AFIR can find pathways starting from two or more reactants toward TSs for their associative reactions. ADDF searches for A X type isomerization and A X + Y type dissocn. pathways, whereas AFIR finds A + B X (+ Y) type associative pathways. Both follow special paths called the ADDF path and the AFIR path, and these tend to pass through near TSs of corresponding reaction pathways, giving approx. TSs. Such approx. TSs can easily be reoptimized to corresponding true TSs by std. geometry optimizations. From these two methods, the authors proposed practical strategies of GRRM. The GRRM strategies were applied to a variety of chem. systems ranging from thermal- and photochem.-reactions in small systems to organometallic- and enzyme-catalysis, from quantum chem. calcns. In this perspective, the authors present an overview of the GRRM strategies and some results of applications. Their practical usage for systematic prediction is also discussed.
- 24Satoh, H.; Oda, T.; Nakakoji, K.; Uno, T.; Tanaka, H.; Iwata, S.; Ohno, K. Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers. J. Chem. Theory Comput. 2016, 12, 5293– 5308, DOI: 10.1021/acs.jctc.6b00439Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFOktr%252FF&md5=a395292cdbf67ed58b06748344d48939Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of D-Glucose ConformersSatoh, Hiroko; Oda, Tomohiro; Nakakoji, Kumiyo; Uno, Takeaki; Tanaka, Hiroaki; Iwata, Satoru; Ohno, KoichiJournal of Chemical Theory and Computation (2016), 12 (11), 5293-5308CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)This paper describes approach that is built upon the potential energy surface (PES)-based conformational anal. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search was achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the min. and TS structures by simply taking into account the math. feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equil. (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalcn. anal. of the deduced r-map is interactively carried out using the RMapViewer software the authors have developed. This paper presents computational details of the PES-based conformational anal. and its application to D-glucose. The calcns. were performed for an isolated glucose mol. in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-D-glucose is composed of 201 Equiv and 435 TS conformers and that for β-D-glucose is composed of 202 Equiv and 371 TS conformers. For the postcalcn. anal. of the conformational r-maps by using the RMapViewer software program the authors found multiple min. energy paths (MEPs) between global min. of 1C4 and 4C1 chair conformations. The anal. using RMapViewer allows us to confirm the thermodn. and kinetic predominance of 4C1 conformations; i.e., the potential energy of the global min. of 4C1 is lower than that of 1C4 (thermodn. predominance) and that the highest energy of those of all the TS structures along a route from 4C1 to 1C4 is lower than that of 1C4 to 4C1 (kinetic predominance).
- 25Maeda, S.; Morokuma, K. A Systematic Method for Locating Transition Structures of A+B→X Type Reactions. J. Chem. Phys. 2010, 132, 241102, DOI: 10.1063/1.3457903Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnvFShtLs%253D&md5=9260f723c31e0b78b5677bb4a89f21d7Communications: A systematic method for locating transition structures of A + B → X type reactionsMaeda, Satoshi; Morokuma, KeijiJournal of Chemical Physics (2010), 132 (24), 241102/1-241102/4CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Search for transition structures (TSs) as first-order saddles is one of the most important tasks in theor. study of chem. reaction. Although automated search has been established either by starting from a local min. (MIN) or by connecting two MINs, there is no systematic method which can locate TSs of A + B → X (+ Y) type reactions starting from sepd. reactants. We propose such an approach for the first time; it was demonstrated to work very well in the SN2, Diels-Alder, and Wittig reactions. (c) 2010 American Institute of Physics.
- 26Maeda, S.; Morokuma, K. Finding Reaction Pathways of Type A+B→X: Toward Systematic Prediction of Reaction Mechanisms. J. Chem. Theory Comput. 2011, 7, 2335– 2345, DOI: 10.1021/ct200290mGoogle Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXosVCktro%253D&md5=85e666d25ec4858a5150bae96893f52aFinding Reaction Pathways of Type A + B → X: Toward Systematic Prediction of Reaction MechanismsMaeda, Satoshi; Morokuma, KeijiJournal of Chemical Theory and Computation (2011), 7 (8), 2335-2345CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)In these five decades, many useful tools have been developed for exploring quantum chem. potential energy surfaces. The success in theor. studies of chem. reaction mechanisms has been greatly supported by these tools. However, systematic prediction of reaction mechanisms starting only from given reactants and catalysts is still very difficult. Toward this goal, we describe the artificial force induced reaction (AFIR) method for automatically finding reaction paths of type A + B → X (+ Y). By imposing an artificial force to given reactants and catalysts, the method can find the reactive sites very efficiently. Further pressing by the artificial force provides approx. transition states and product structures, which can be easily reoptimized to the corresponding true ones. This procedure can be executed very efficiently just by minimizing a single function called the AFIR function. All important reaction paths can be found by repeating this cycle starting from many initial orientations. We also discuss perspectives of automated reaction path search methods toward the above goal.
- 27Maeda, S.; Taketsugu, T.; Morokuma, K. Exploring Transition State Structures for Intramolecular Pathways by the Artificial Force Induced Reaction Method. J. Comput. Chem. 2014, 35, 166– 173, DOI: 10.1002/jcc.23481Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslaqs77J&md5=18ee5becec9b21d0bdcef4d37b50a48dExploring transition state structures for intramolecular pathways by the artificial force induced reaction methodMaeda, Satoshi; Taketsugu, Tetsuya; Morokuma, KeijiJournal of Computational Chemistry (2014), 35 (2), 166-173CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Finding all required transition state (TS) structures is an important but hard task in theor. study of complex reaction mechanisms. An efficient automated TS search method, artificial force induced reaction (AFIR), was extended to intramol. reactions. The AFIR method was developed for intermol. associative pathways between two or more reactants. Although it also was applied to intramol. reactions by dividing mols. manually into fragments, the fragmentation scheme was not automated. The authors propose an automated fragmentation scheme. Using this fragmentation scheme and the AFIR method, a fully automated search algorithm for intramol. pathways is introduced. This version for intramol. reactions is called single-component AFIR (SC-AFIR), to distinguish it from multicomponent AFIR for intermol. reactions. SC-AFIR was tested with two reactions, the Claisen rearrangement and the first step of cobalt-catalyzed hydroformylation, and successfully located all important pathways reported in the literature. © 2013 Wiley Periodicals, Inc.
- 28Maeda, S.; Harabuchi, Y.; Takagi, M.; Taketsugu, T.; Morokuma, K. Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy Surfaces. Chem. Rec. 2016, 16, 2232– 2248, DOI: 10.1002/tcr.201600043Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XptV2iurg%253D&md5=fb8514d68f9fefc53f4d5f9ad8e19e06Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy SurfacesMaeda, Satoshi; Harabuchi, Yu; Takagi, Makito; Taketsugu, Tetsuya; Morokuma, KeijiChemical Record (2016), 16 (5), 2232-2248CODEN: CRHEAK; ISSN:1528-0691. (Wiley-VCH Verlag GmbH & Co. KGaA)In this account, a tech. overview of the artificial force induced reaction (AFIR) method is presented. The AFIR method is one of the automated reaction-path search methods developed by the authors, and has been applied extensively to a variety of chem. reactions, such as organocatalysis, organometallic catalysis, and photoreactions. There are two modes in the AFIR method, i.e., a multicomponent mode and a single-component mode. The former has been applied to bimol. and multicomponent reactions and the latter to unimol. isomerization and dissocn. reactions. Five numerical examples are presented for an Aldol reaction, a Claisen rearrangement, a Co-catalyzed hydroformylation, a fullerene structure search, and a nonradiative decay path search in an electronically excited naphthalene mol. Finally, possible applications of the AFIR method are discussed.
- 29Yoshimura, T.; Maeda, S.; Taketsugu, T.; Sawamura, M.; Morokuma, K.; Mori, S. Exploring the Full Catalytic Cycle of Rhodium(I)–BINAP-Catalysed Isomerisation of Allylic Amines: A Graph Theory Approach for Path Optimisation. Chem. Sci. 2017, 8, 4475– 4488, DOI: 10.1039/C7SC00401JGoogle Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntlWgt7s%253D&md5=c2ab51df0053f782bc9e9f5323ec2358Exploring the full catalytic cycle of rhodium(I)-BINAP-catalysed isomerisation of allylic amines: a graph theory approach for path optimisationYoshimura, Takayoshi; Maeda, Satoshi; Taketsugu, Tetsuya; Sawamura, Masaya; Morokuma, Keiji; Mori, SeijiChemical Science (2017), 8 (6), 4475-4488CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)We explored the reaction mechanism of the cationic rhodium(I)-BINAP complex catalyzed isomerization of allylic amines using the artificial force induced reaction method with the global reaction route mapping strategy, which enabled us to search for various reaction paths without assumption of transition states. The entire reaction network was reproduced in the form of a graph, and reasonable paths were selected from the complicated network using Prim's algorithm. As a result, a new dissociative reaction mechanism was proposed. Our comprehensive reaction path search provided rationales for the E/Z and S/R selectivities of the stereoselective reaction.
- 30Puripat, M.; Ramozzi, R.; Hatanaka, M.; Parasuk, W.; Parasuk, V.; Morokuma, K. The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent Reaction. J. Org. Chem. 2015, 80, 6959– 6967, DOI: 10.1021/acs.joc.5b00407Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVans7nM&md5=7f6185df4c8e5c3802f013bc36a694c7The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent ReactionPuripat, Maneeporn; Ramozzi, Romain; Hatanaka, Miho; Parasuk, Waraporn; Parasuk, Vudhichai; Morokuma, KeijiJournal of Organic Chemistry (2015), 80 (14), 6959-6967CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)The recently developed artificial force induced reaction (AFIR) method was applied to search systematically all possible multicomponent pathways for the Biginelli reaction mechanism. The most favorable pathway starts with the condensation of the urea and benzaldehyde, followed by the addn. of Et acetoacetate. Remarkably, a second urea mol. catalyzes nearly every step of the reaction. Thus, the Biginelli reaction is a urea-catalyzed multicomponent reaction. The reaction mechanism was found to be identical in both protic and aprotic solvents.
- 31Saitta, A. M.; Saija, F. Miller Experiments in Atomistic Computer Simulations. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 13768– 13773, DOI: 10.1073/pnas.1402894111Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFSju7nN&md5=711514af5c0a3a8d6d0a226d29be2d8bMiller experiments in atomistic computer simulationsSaitta, Antonino Marco; Saija, FranzProceedings of the National Academy of Sciences of the United States of America (2014), 111 (38), 13768-13773CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The celebrated Miller expts. reported on the spontaneous formation of amino acids from a mixt. of simple mols. reacting under an elec. discharge, giving birth to the research field of prebiotic chem. However, the chem. reactions involved in those expts. have never been studied at the at. level. Here the authors report on, to the authors' knowledge, the first ab initio computer simulations of Miller-like expts. in the condensed phase. The authors' study, based on the recent method of treatment of aq. systems under elec. fields and on metadynamics anal. of chem. reactions, shows that glycine spontaneously forms from mixts. of simple mols. once an elec. field is switched on and identifies formic acid and formamide as key intermediate products of the early steps of the Miller reactions, and the crucible of formation of complex biol. mols.
- 32Wang, L.-P.; Titov, A.; McGibbon, R.; Liu, F.; Pande, V. S.; Martínez, T. J. Discovering Chemistry with an Ab Initio Nanoreactor. Nat. Chem. 2014, 6, 1044– 1048, DOI: 10.1038/nchem.2099Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVGitbnI&md5=201fe998c04f0c9b9a7aa6ebf329a2c5Discovering chemistry with an ab initio nanoreactorWang, Lee-Ping; Titov, Alexey; McGibbon, Robert; Liu, Fang; Pande, Vijay S.; Martinez, Todd J.Nature Chemistry (2014), 6 (12), 1044-1048CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)Chem. understanding is driven by the exptl. discovery of new compds. and reactivity, and is supported by theory and computation that provide detailed phys. insight. Although theor. and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodol. and computational advances harken the advent of their principal role in discovery. Here, we report the development and application of the ab initio nanoreactor-a highly accelerated first-principles mol. dynamics simulation of chem. reactions that discovers new mols. and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor, we show new pathways for glycine synthesis from primitive compds. proposed to exist on the early Earth, which provide new insight into the classic Urey-Miller expt. These results highlight the emergence of theor. and computational chem. as a tool for discovery, in addn. to its traditional role of interpreting exptl. findings.
- 33Wang, L.-P.; McGibbon, R. T.; Pande, V. S.; Martinez, T. J. Automated Discovery and Refinement of Reactive Molecular Dynamics Pathways. J. Chem. Theory Comput. 2016, 12, 638– 649, DOI: 10.1021/acs.jctc.5b00830Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVGku7nL&md5=6a731baa0767e0105247b156289fe8baAutomated Discovery and Refinement of Reactive Molecular Dynamics PathwaysWang, Lee-Ping; McGibbon, Robert T.; Pande, Vijay S.; Martinez, Todd J.Journal of Chemical Theory and Computation (2016), 12 (2), 638-649CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We describe a flexible and broadly applicable energy refinement method, "nebterpolation," for identifying and characterizing the reaction events in a mol. dynamics (MD) simulation. The new method is applicable to ab initio simulations with hundreds of atoms contg. complex and multimol. reaction events. A key aspect of nebterpolation is smoothing of the reactive MD trajectory in internal coordinates to initiate the search for the reaction path on the potential energy surface. We apply nebterpolation to analyze the reaction events in an ab initio nanoreactor simulation that discovers new mols. and mechanisms, including a C-C coupling pathway for glycolaldehyde synthesis. We find that the new method, which incorporates information from the MD trajectory that connects reactants with products, produces a dramatically distinct set of min. energy paths compared to existing approaches that start from information for the reaction end points alone. The energy refinement method described here represents a key component of an emerging simulation paradigm where mol. dynamics simulations are applied to discover the possible reaction mechanisms.
- 34Meuwly, M. Reactive Molecular Dynamics: From Small Molecules to Proteins. WIREs Comput. Mol. Sci. 2018, 0, e1386 DOI: 10.1002/wcms.1386
- 35van Duin, A. C. T.; Dasgupta, S.; Lorant, F.; Goddard, W. A. ReaxFF: A Reactive Force Field for Hydrocarbons. J. Phys. Chem. A 2001, 105, 9396– 9409, DOI: 10.1021/jp004368uGoogle Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFChu78%253D&md5=ea59efc08d5e135745df988f2006a7fdReaxFF: A Reactive Force Field for Hydrocarbonsvan Duin, Adri C. T.; Dasgupta, Siddharth; Lorant, Francois; Goddard, William A., IIIJournal of Physical Chemistry A (2001), 105 (41), 9396-9409CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)To make practical the mol. dynamics simulation of large scale reactive chem. systems (1000 s of atoms), the authors developed ReaxFF, a force field for reactive systems. ReaxFF uses a general relation between bond distance and bond order on one hand and between bond order and bond energy however, that leads to proper dissocn. of bonds to sepd. atoms. Other valence terms present in the force field (angle and torsion) are defined in terms of the same bond orders so that all these terms go to zero smoothly as bonds break. In addn., ReaxFF has Coulomb and Morse (van der Waals) potentials to describe nonbond interactions between all atoms (no exclusions). These nonbond interactions are shielded at short range so that the Coulomb and van der Waals interactions become const. as Rij → 0. The authors report here the ReaxFF for hydrocarbons. The parameters were derived from quantum chem. calcns. on bond dissocn. and reactions of small mols. plus heat of formation and geometry data for a no. of stable hydrocarbon compds. The ReaxFF provides a good description of these data. Generally, the results are of an accuracy similar or better than PM3, while ReaxFF is ∼100 times faster. In turn, the PM3 is ∼100 times faster than the QC calcns. Thus, with ReaxFF the authors hope to be able to study complex reactions in hydrocarbons.
- 36Döntgen, M.; Przybylski-Freund, M.-D.; Kröger, L. C.; Kopp, W. A.; Ismail, A. E.; Leonhard, K. Automated Discovery of Reaction Pathways, Rate Constants, and Transition States Using Reactive Molecular Dynamics Simulations. J. Chem. Theory Comput. 2015, 11, 2517– 2524, DOI: 10.1021/acs.jctc.5b00201Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28vjt1Gjtg%253D%253D&md5=7f936903e2258f886ccce3fc8fef0996Automated discovery of reaction pathways, rate constants, and transition states using reactive molecular dynamics simulationsDontgen Malte; Przybylski-Freund Marie-Dominique; Kroger Leif C; Kopp Wassja A; Ismail Ahmed E; Leonhard KaiJournal of chemical theory and computation (2015), 11 (6), 2517-24 ISSN:.We provide a methodology for deducing quantitative reaction models from reactive molecular dynamics simulations by identifying, quantifying, and evaluating elementary reactions of classical trajectories. Simulations of the inception stage of methane oxidation are used to demonstrate our methodology. The agreement of pathways and rates with available literature data reveals the potential of reactive molecular dynamics studies for developing quantitative reaction models.
- 37Fischer, S.; Karplus, M. Conjugate Peak Refinement: An Algorithm for Finding Reaction Paths and Accurate Transition States in Systems with Many Degrees of Freedom. Chem. Phys. Lett. 1992, 194, 252– 261, DOI: 10.1016/0009-2614(92)85543-JGoogle Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XltFSqtrk%253D&md5=938aae7d35f6942adbd76bf19c19cf9dConjugate peak refinement: an algorithm for finding reaction paths and accurate transition states in systems with many degrees of freedomFischer, Stefan; Karplus, MartinChemical Physics Letters (1992), 194 (3), 252-61CODEN: CHPLBC; ISSN:0009-2614.An algorithm is presented for detg. multidimensional reaction coordinates between two known conformers. Only the energy function and its gradient are required. The resulting paths follow the adiabatic energy valleys and have energy max. that are true saddle points, which can be multiple along each path. The method is suitable for the study of complex isomerization reactions, including allosteric transitions in proteins and more general conformational changes of macromols.
- 38Florián, J.; Goodman, M. F.; Warshel, A. Computer Simulation of the Chemical Catalysis of DNA Polymerases: Discriminating between Alternative Nucleotide Insertion Mechanisms for T7 DNA Polymerase. J. Am. Chem. Soc. 2003, 125, 8163– 8177, DOI: 10.1021/ja028997oGoogle Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXksFWgsbY%253D&md5=98029baf5458f072872a0746ea5ab990Computer simulation of the chemical catalysis of DNA polymerases: Discriminating between alternative nucleotide insertion mechanisms for T7 DNA polymeraseFlorian, Jan; Goodman, Myron F.; Warshel, AriehJournal of the American Chemical Society (2003), 125 (27), 8163-8177CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Understanding the chem. step in the catalytic reaction of DNA polymerases is essential for elucidating the mol. basis of the fidelity of DNA replication. The present work evaluates the free energy surface for the nucleotide transfer reaction of T7 polymerase by free energy perturbation/empirical valence bond (FEP/EVB) calcns. A key aspect of the enzyme simulation is a comparison of enzymic free energy profiles with the corresponding ref. reactions in water using the same computational methodol., thereby enabling a quant. est. for the free energy of the nucleotide insertion reaction. The reaction is driven by the FEP/EVB methodol. between valence bond structures representing the reactant, pentacovalent intermediate, and the product states. This pathway corresponds to three microscopic chem. steps, deprotonation of the attacking group, a nucleophilic attack on the Pα atom of the dNTP substrate, and departure of the leaving group. Three different mechanisms for the first microscopic step, the generation of the RO- nucleophile from the 3'-OH hydroxyl of the primer, are examd.: (i) proton transfer to the bulk solvent, (ii) proton transfer to one of the ionic oxygens of the Pα phosphate group, and (iii) proton transfer to the ionized Asp 654 residue. The most favorable reaction mechanism in T7 pol is predicted to involve the proton transfer to Asp 654. This finding sheds light on the long standing issue of the actual role of conserved aspartates. The structural preorganization that helps to catalyze the reaction is also considered and analyzed. The overall calcd. mechanism consists of three subsequent steps with a similar activation free energy of about 12 kcal/mol. The similarity of the activation barriers of the three microscopic chem. steps indicates that the T7 polymerase may select against the incorrect dNTP substrate by raising any of these barriers. The relative height of these barriers comparing right and wrong dNTP substrates should therefore be a primary focus of future computational studies of the fidelity of DNA polymerases.
- 39Garcia-Viloca, M.; Gao, J.; Karplus, M.; Truhlar, D. G. How Enzymes Work: Analysis by Modern Rate Theory and Computer Simulations. Science 2004, 303, 186– 195, DOI: 10.1126/science.1088172Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhtlGhug%253D%253D&md5=35766752530af526c8bdc99774a8e9daHow enzymes work: Analysis by modern rate theory and computer simulationsGarcia-Viloca, Mireia; Gao, Jiali; Karplus, Martin; Truhlar, Donald G.Science (Washington, DC, United States) (2004), 303 (5655), 186-195CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review and discussion. Advances in transition state theory and computer simulations are providing new insights into the sources of enzyme catalysis. Both the lowering of the activation free energy and changes in the generalized transmission coeff. (recrossing of the transition state, tunneling, and nonequil. contributions) can play a role. A framework for understanding these effects is presented, and the contributions of the different factors, as illustrated by specific enzymes, are identified and quantified by computer simulations. The resulting understanding of enzyme catalysis is used to comment on alternative proposals of how enzymes work.
- 40Imhof, P.; Fischer, S.; Smith, J. C. Catalytic Mechanism of DNA Backbone Cleavage by the Restriction Enzyme EcoRV: A Quantum Mechanical/Molecular Mechanical Analysis. Biochemistry 2009, 48, 9061– 9075, DOI: 10.1021/bi900585mGoogle Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtV2mtbvP&md5=88ce54a5f9131bc8ad11b1dbd07f8e6eCatalytic Mechanism of DNA Backbone Cleavage by the Restriction Enzyme EcoRV: A Quantum Mechanical/Molecular Mechanical AnalysisImhof, Petra; Fischer, Stefan; Smith, Jeremy C.Biochemistry (2009), 48 (38), 9061-9075CODEN: BICHAW; ISSN:0006-2960. (American Chemical Society)Endonucleases, such as the restriction enzyme EcoRV, cleave the DNA backbone at a specific recognition sequence. We have investigated the catalytic mechanism of backbone phosphodiester hydrolysis by the restriction enzyme EcoRV by means of hybrid quantum mech./mol. mech. calcns. An exhaustive computation of different reaction pathways is performed, thus generating a network of pathways. Comparison of the computed (AM1d/MM) enzymic reaction pathways with an analogous mechanism for small-mol. model systems [AM1/d and B3LYP/6-31++G(d,p)] reveals that the transition barriers for associative hydrolysis, which is more probable in the model systems, are not lowered by the enzyme. Instead, a reaction mechanism which has mostly dissociative character is more likely. The protein environment is tuned to significantly electrostatically stabilize the transition state structures. The direct catalytic impact of essential residues is detd. The magnesium metal ion activates a water mol., thus facilitating protonation of the leaving group. A redn. of the coordination no. of the magnesium metal ion from six to four upon the positioning of the attacking water mol. explains why larger metal ions, such as calcium, are not catalytically active. The nucleophile is generated by the transfer of a proton from the attacking water mol. to a carboxylic oxygen atom of aspartate 90. The catalytic effect of lysine 92 involves proper positioning of the scissile phosphate group and, more importantly, stabilization of the metaphosphate intermediate in an orientation optimal for attack of the nucleophile.
- 41Reidelbach, M.; Betz, F.; Mäusle, R. M.; Imhof, P. Proton Transfer Pathways in an Aspartate-Water Cluster Sampled by a Network of Discrete States. Chem. Phys. Lett. 2016, 659, 169– 175, DOI: 10.1016/j.cplett.2016.07.021
- 42Imhof, P. A. Networks Approach to Modeling Enzymatic Reactions. Methods Enzymol. 2016, 578, 249– 271, DOI: 10.1016/bs.mie.2016.05.025
- 43Senn, H. M.; Thiel, W. QM/MM Methods for Biological Systems. Top. Curr. Chem. 2007, 268, 173– 290, DOI: 10.1007/128_2006_084Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjvVOlt7c%253D&md5=bf5f07823db75b3e05018ed47b70d2c1QM/MM methods for biological systemsSenn, Hans Martin; Thiel, WalterTopics in Current Chemistry (2007), 268 (Atomistic Approaches in Modern Biology), 173-290CODEN: TPCCAQ; ISSN:0340-1022. (Springer GmbH)A review. Thirty years after the seminal contribution by Warshel and Levitt, we review the state of the art of combined quantum-mechanics/mol.-mechanics (QM/MM) methods, with a focus on biomol. systems. We provide a detailed overview of the methodol. of QM/MM calcns. and their use within optimization and simulation schemes. A tabular survey of recent applications, mostly to enzymic reactions, is given.
- 44Senn, H. M.; Thiel, W. QM/MM Studies of Enzymes. Curr. Opin. Chem. Biol. 2007, 11, 182– 187, DOI: 10.1016/j.cbpa.2007.01.684Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjvFegurw%253D&md5=361cc5b164e23e5a71dac6f4bbf7d673QM/MM studies of enzymesSenn, Hans Martin; Thiel, WalterCurrent Opinion in Chemical Biology (2007), 11 (2), 182-187CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)A review. Combined quantum-mechanics/mol.-mechanics (QM/MM) methods are making rapid progress both methodol. and with respect to their range of application. Mechanistic studies on enzymes, including contributions toward the understanding of enzyme catalysis, continue to be a major target. They are joined by calcns. of pKa values, redox properties, ground- and excited-state spectroscopic parameters, and excited-state dynamics. Methodol. advances include improved QM/MM schemes, in particular new approaches for an effective treatment of the QM-MM electrostatic interactions, and the incorporation of new efficient and accurate QM methods in QM/MM schemes.
- 45Senn, H. M.; Thiel, W. QM/MM Methods for Biomolecular Systems. Angew. Chem., Int. Ed. 2009, 48, 1198– 1229, DOI: 10.1002/anie.200802019Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXitFOqs7g%253D&md5=c51da58b0525651c71f9c393a79023beQM/MM methods for biomolecular systemsSenn, Hans Martin; Thiel, WalterAngewandte Chemie, International Edition (2009), 48 (7), 1198-1229CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Combined quantum-mechanics/mol.-mechanics (QM/MM) approaches have become the method of choice for modeling reactions in biomol. systems. Quantum-mech. (QM) methods are required for describing chem. reactions and other electronic processes, such as charge transfer or electronic excitation. However, QM methods are restricted to systems of up to a few hundred atoms. However, the size and conformational complexity of biopolymers calls for methods capable of treating up to several 100,000 atoms and allowing for simulations over time scales of tens of nanoseconds. This is achieved by highly efficient, force-field-based mol. mechanics (MM) methods. Thus to model large biomols. the logical approach is to combine the two techniques and, to use a QM method for the chem. active region (e.g., substrates and co-factors in an enzymic reaction) and an MM treatment for the surroundings (e.g., protein and solvent). The resulting schemes are commonly referred to as combined or hybrid QM/MM methods. They enable the modeling of reactive biomol. systems at a reasonable computational effort while providing the necessary accuracy.
- 46Huber, T.; Torda, A. E.; van Gunsteren, W. F. Local Elevation: A Method for Improving the Searching Properties of Molecular Dynamics Simulation. J. Comput.-Aided Mol. Des. 1994, 8, 695– 708, DOI: 10.1007/BF00124016Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXjtVOnsrw%253D&md5=8d352c5753f9870081d4851ff12e58cdLocal elevation: a method for improving the searching properties of molecular dynamics simulationHuber, Thomas; Torda, Andrew E.; van Gunsteren, Wilfred F.Journal of Computer-Aided Molecular Design (1994), 8 (6), 695-708CODEN: JCADEQ; ISSN:0920-654X. (ESCOM)The concept of memory has been introduced into a mol. dynamics algorithm. This was done so as to persuade a mol. system to visit new areas of conformational space rather than be confined to a small no. of low-energy regions. The method is demonstrated on a simple model system and the 11-residue cyclic peptide cyclosporin A. For comparison, calcns. were also performed using simulated temp. annealing and a potential energy annealing scheme. Although the method can only be applied to systems with a small no. of degrees of freedom, it offers the chance to generate a multitude of different low-energy structures, where other methods only give a single one or few. This is clearly important in problems such as drug design, where one is interested in the conformational spread of a system.
- 47Laio, A.; Parrinello, M. Escaping Free-Energy Minima. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 12562– 12566, DOI: 10.1073/pnas.202427399Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XnvFGiurc%253D&md5=48d5bc7436f3ef9d78369671e70fa608Escaping free-energy minimaLaio, Alessandro; Parrinello, MicheleProceedings of the National Academy of Sciences of the United States of America (2002), 99 (20), 12562-12566CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)We introduce a powerful method for exploring the properties of the multidimensional free energy surfaces (FESs) of complex many-body systems by means of coarse-grained non-Markovian dynamics in the space defined by a few collective coordinates. A characteristic feature of these dynamics is the presence of a history-dependent potential term that, in time, fills the min. in the FES, allowing the efficient exploration and accurate detn. of the FES as a function of the collective coordinates. We demonstrate the usefulness of this approach in the case of the dissocn. of a NaCl mol. in water and in the study of the conformational changes of a dialanine in soln.
- 48Christen, M.; van Gunsteren, W. F. On Searching in, Sampling of, and Dynamically Moving through Conformational Space of Biomolecular Systems: A Review. J. Comput. Chem. 2008, 29, 157– 166, DOI: 10.1002/jcc.20725Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2sjktVOitQ%253D%253D&md5=c508200635d58b25f5ee678a9c016f87On searching in, sampling of, and dynamically moving through conformational space of biomolecular systems: A reviewChristen Markus; van Gunsteren Wilfred FJournal of computational chemistry (2008), 29 (2), 157-66 ISSN:0192-8651.Methods to search for low-energy conformations, to generate a Boltzmann-weighted ensemble of configurations, or to generate classical-dynamical trajectories for molecular systems in the condensed liquid phase are briefly reviewed with an eye to application to biomolecular systems. After having chosen the degrees of freedom and method to generate molecular configurations, the efficiency of the search or sampling can be enhanced in various ways: (i) efficient calculation of the energy function and forces, (ii) application of a plethora of search enhancement techniques, (iii) use of a biasing potential energy term, and (iv) guiding the sampling using a reaction or transition pathway. The overview of the available methods should help the reader to choose the combination that is most suitable for the biomolecular system, degrees of freedom, interaction function, and molecular or thermodynamic properties of interest.
- 49Bernardi, R. C.; Melo, M. C. R.; Schulten, K. Enhanced Sampling Techniques in Molecular Dynamics Simulations of Biological Systems. Biochim. Biophys. Acta, Gen. Subj. 2015, 1850, 872– 877, DOI: 10.1016/j.bbagen.2014.10.019Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVanurbN&md5=44e3ac1aa042c35ee08aa86a6a63e78eEnhanced sampling techniques in molecular dynamics simulations of biological systemsBernardi, Rafael C.; Melo, Marcelo C. R.; Schulten, KlausBiochimica et Biophysica Acta, General Subjects (2015), 1850 (5), 872-877CODEN: BBGSB3; ISSN:0304-4165. (Elsevier B.V.)A review. Mol. dynamics has emerged as an important research methodol. covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local min. sepd. by high-energy barriers, which govern the biomol. motion. In the past few decades methods have been developed that address the sampling problem, such as replica-exchange mol. dynamics, metadynamics and simulated annealing. Here the authors present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Enhanced sampling methods have been employed for a broad range of biol. systems and the choice of a suitable method is connected to biol. and phys. characteristics of the system, in particular system size. While metadynamics and replica-exchange mol. dynamics are the most adopted sampling methods to study biomol. dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromol. complexes. Mol. dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biol. function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of mol. dynamics.
- 50Shim, J.; MacKerell, A. D., Jr. Computational Ligand-Based Rational Design: Role of Conformational Sampling and Force Fields in Model Development. MedChemComm 2011, 2, 356– 370, DOI: 10.1039/c1md00044fGoogle Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1Kht7c%253D&md5=70d822d1ca2faa484f723fb109597b77Computational ligand-based rational design: role of conformational sampling and force fields in model developmentShim, Jihyun; MacKerell, Alexander D., Jr.MedChemComm (2011), 2 (5), 356-370CODEN: MCCEAY; ISSN:2040-2503. (Royal Society of Chemistry)A review. A significant no. of drug discovery efforts are based on natural products or high throughput screens from which compds. showing potential therapeutic effects are identified without knowledge of the target mol. or its 3D structure. In such cases computational ligand-based drug design (LBDD) can accelerate the drug discovery processes. LBDD is a general approach to elucidate the relationship of a compd.'s structure and physicochem. attributes to its biol. activity. The resulting structure-activity relationship (SAR) may then act as the basis for the prediction of compds. with improved biol. attributes. LBDD methods range from pharmacophore models identifying essential features of ligands responsible for their activity, quant. structure-activity relationships (QSAR) yielding quant. ests. of activities based on physiochem. properties, and to similarity searching, which explores compds. with similar properties as well as various combinations of the above. A no. of recent LBDD approaches involve the use of multiple conformations of the ligands being studied. One of the basic components to generate multiple conformations in LBDD is mol. mechanics (MM), which apply an empirical energy function to relate conformation to energies and forces. The collection of conformations for ligands is then combined with functional data using methods ranging from regression anal. to neural networks, from which the SAR is detd. Accordingly, for effective application of LBDD for SAR detns. it is important that the compds. be accurately modelled such that the appropriate range of conformations accessible to the ligands is identified. Such accurate modeling is largely based on use of the appropriate empirical force field for the mols. being investigated and the approaches used to generate the conformations. The present chapter includes a brief overview of currently used SAR methods in LBDD followed by a more detailed presentation of issues and limitations assocd. with empirical energy functions and conformational sampling methods.
- 51Ballard, A. J.; Martiniani, S.; Stevenson, J. D.; Somani, S.; Wales, D. J. Exploiting the Potential Energy Landscape to Sample Free Energy. WIREs Comput. Mol. Sci. 2015, 5, 273– 289, DOI: 10.1002/wcms.1217
- 52De Vivo, M.; Masetti, M.; Bottegoni, G.; Cavalli, A. Role of Molecular Dynamics and Related Methods in Drug Discovery. J. Med. Chem. 2016, 59, 4035– 4061, DOI: 10.1021/acs.jmedchem.5b01684Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlWksLs%253D&md5=b3d8a4fb5705a3555c2bb2a962420396Role of Molecular Dynamics and Related Methods in Drug DiscoveryDe Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, AndreaJournal of Medicinal Chemistry (2016), 59 (9), 4035-4061CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society)Mol. dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate est. of the thermodn. and kinetics assocd. with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theor. background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water mols. in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates.
- 53Tsujishita, H.; Hirono, S. Camdas: An Automated Conformational Analysis System Using Molecular Dynamics. J. Comput.-Aided Mol. Des. 1997, 11, 305– 315, DOI: 10.1023/A:1007964913898
- 54Wilson, S. R.; Cui, W.; Moskowitz, J. W.; Schmidt, K. E. Applications of Simulated Annealing to the Conformational Analysis of Flexible Molecules. J. Comput. Chem. 1991, 12, 342– 349, DOI: 10.1002/jcc.540120307Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3MXitVKhsLw%253D&md5=7ca487c05c358c760a76eed13145b5deApplications of simulated annealing to the conformational analysis of flexible moleculesWilson, Stephen R.; Cui, Weili; Moskowitz, Jules W.; Schmidt, Kevin E.Journal of Computational Chemistry (1991), 12 (3), 342-9CODEN: JCCHDD; ISSN:0192-8651.A soln. to the global min. problem which uses the simulated annealing algorithm of Kirkpatrick is described. This method is a Metropolis (e-ΔE/kT) Monte Carlo sampling of conformation space with simultaneous constraint of the search by lowering the temp. T so that the search converges on the global min. The Anneal-Conformer program has been extensively tested with peptides and org. mols. using either the Amber or MM2 force fields. A history file of the simulated annealing process allows reconstruction of the random walk in conformation space for subsequent examn. Thus plots of distance and dihedral angle changes during the search for the global min. can be examd. to deduce mol. shape and flexibility. A sep. program Conf-Gen reads the history file and exts. all low energy conformations visited during the run.
- 55Sperandio, O.; Souaille, M.; Delfaud, F.; Miteva, M. A.; Villoutreix, B. O. MED-3DMC: A New Tool to Generate 3D Conformation Ensembles of Small Molecules with a Monte Carlo Sampling of the Conformational Space. Eur. J. Med. Chem. 2009, 44, 1405– 1409, DOI: 10.1016/j.ejmech.2008.09.052Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjtVSjtLw%253D&md5=bc3b0f5ea5b23da6eec7048f39081448MED-3DMC: A new tool to generate 3D conformation ensembles of small molecules with a Monte Carlo sampling of the conformational spaceSperandio, Olivier; Souaille, Marc; Delfaud, Francois; Miteva, Maria A.; Villoutreix, Bruno O.European Journal of Medicinal Chemistry (2009), 44 (4), 1405-1409CODEN: EJMCA5; ISSN:0223-5234. (Elsevier Masson SAS)Obtaining an efficient sampling of the low to medium energy regions of a ligand conformational space is of primary importance for getting insight into relevant binding modes of drug candidates, or for the screening of rigid mol. entities on the basis of a predefined pharmacophore or for rigid body docking. Here, we report the development of a new computer tool that samples the conformational space by using the Metropolis Monte Carlo algorithm combined with the MMFF94 van der Waals energy term. The performances of the program have been assessed on 86 drug-like mols. that resulted from an ADME/tox profiling applied on cocrystalized small mols. and were compared with the program Omega on the same dataset. Our program has also been assessed on the 85 mols. of the Astex diverse set. Both test sets show convincing performance of our program at sampling the conformational space.
- 56Grebner, C.; Becker, J.; Stepanenko, S.; Engels, B. Efficiency of Tabu-Search-Based Conformational Search Algorithms. J. Comput. Chem. 2011, 32, 2245– 2253, DOI: 10.1002/jcc.21807
- 57Shang, C.; Liu, Z.-P. Stochastic Surface Walking Method for Structure Prediction and Pathway Searching. J. Chem. Theory Comput. 2013, 9, 1838– 1845, DOI: 10.1021/ct301010bGoogle Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOlt7c%253D&md5=ff2585b886e8cc63d4443934f5317048Stochastic Surface Walking Method for Structure Prediction and Pathway SearchingShang, Cheng; Liu, Zhi-PanJournal of Chemical Theory and Computation (2013), 9 (3), 1838-1845CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We propose an unbiased general-purpose potential energy surface (PES) searching method for both the structure and the pathway prediction of a complex system. The method is based on the idea of bias-potential-driven dynamics and Metropolis Monte Carlo. A central feature of the method is able to perturb smoothly a structural configuration toward a new configuration and simultaneously has the ability to surmount the high barrier in the path. We apply the method for locating the global min. (GM) of short-ranged Morse clusters up to 103 atoms starting from a random structure without using extra information from the system. In addn. to GM searching, the method can identify the pathways for chem. reactions with large dimensionality, as demonstrated in a nanohelix transformation contg. 222 degrees of freedoms.
- 58Zhang, X.-J.; Shang, C.; Liu, Z.-P. From Atoms to Fullerene: Stochastic Surface Walking Solution for Automated Structure Prediction of Complex Material. J. Chem. Theory Comput. 2013, 9, 3252– 3260, DOI: 10.1021/ct400238jGoogle Scholar58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXosVegsr0%253D&md5=0e94b080ff99b33134c703b183357f15From Atoms to Fullerene: Stochastic Surface Walking Solution for Automated Structure Prediction of Complex MaterialZhang, Xiao-Jie; Shang, Cheng; Liu, Zhi-PanJournal of Chemical Theory and Computation (2013), 9 (7), 3252-3260CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)It is of general concern whether the automated structure prediction of unknown material without recourse to any knowledge from expt. is ever possible considering the daunting complexity of potential energy surface (PES) of material. Here we demonstrate that the stochastic surface walking (SSW) method can be a general and promising soln. to this ultimate goal, which is applied to assemble carbon fullerenes contg. up to 100 atoms (including 60, 70, 76, 78, 80, 84, 90, 96, and 100 atoms) from randomly distributed atoms, a long-standing challenge in global optimization. Combining the SSW method with a parallel replica exchange algorithm, we can locate the global min. (GM) of these large fullerenes efficiently without being trapped in numerous energy-nearly degenerate isomers. Detailed analyses on the SSW trajectories allow us to rationalize how and why the SSW method is able to explore the highly complex PES, which highlights the abilities of SSW method for surmounting the high barrier and the preference of SSW trajectories to the low energy pathways. The work demonstrates that the parallel SSW method is a practical tool for predicting unknown materials.
- 59Shang, C.; Zhang, X.-J.; Liu, Z.-P. Stochastic Surface Walking Method for Crystal Structure and Phase Transition Pathway Prediction. Phys. Chem. Chem. Phys. 2014, 16, 17845– 17856, DOI: 10.1039/C4CP01485EGoogle Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFyms7jE&md5=c5dc152fa492d8978d79bbcf35313753Stochastic surface walking method for crystal structure and phase transition pathway predictionShang, Cheng; Zhang, Xiao-Jie; Liu, Zhi-PanPhysical Chemistry Chemical Physics (2014), 16 (33), 17845-17856CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The detn. of crystal structures and the solid-to-solid phase transition mechanisms are two important and related subjects in material science. Here we develop an unbiased general-purpose potential energy surface (PES) searching method, namely, SSW-crystal method, for prediction of both the crystal structure and the crystal phase transition pathway. The SSW-crystal method features with stochastic surface walking (SSW) via repeated small structural perturbation by taking into account the second deriv. information on both the lattice and the atom degrees of freedom. The SSW-crystal method is capable of overcoming the high barrier of phase transition and identifying the desirable phase transition reaction coordinates. By applying the SSW-crystal method to a set of examples, including SiO2 crystal up to 162 atoms per cell, Lennard-Jones model crystals up to 256 atoms, ternary SrTiO3 crystal of 50 atoms and the rutile-to-anatase TiO2 phase transition, we show that the SSW-crystal method can efficiently locate the global min. (GM) from random initial structures without a priori knowledge of the system, and also allows for exhaustive sampling of the phase transition pathways, from which the lowest energy pathway can be obtained.
- 60Zhang, X.-J.; Liu, Z.-P. Reaction Sampling and Reactivity Prediction Using the Stochastic Surface Walking Method. Phys. Chem. Chem. Phys. 2015, 17, 2757– 2769, DOI: 10.1039/C4CP04456HGoogle Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVSgur3F&md5=c5ac6082903ea35d005a1e00ab73febeReaction sampling and reactivity prediction using the stochastic surface walking methodZhang, Xiao-Jie; Liu, Zhi-PanPhysical Chemistry Chemical Physics (2015), 17 (4), 2757-2769CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The prediction of chem. reactivity and thus the design of new reaction systems are the key challenges in chem. Here, we develop an unbiased general-purpose reaction sampling method, the stochastic surface walking based reaction sampling (SSW-RS) method, and show that the new method is a promising soln. for reactivity prediction of complex reaction systems. The SSW-RS method is capable of sampling both the configuration space of the reactant and the reaction space of pathways, owing to the combination of two recently developed theor. methods, namely, the stochastic surface walking (SSW) method for potential energy surface (PES) exploration and the double-ended surface walking (DESW) method for building pathways. By integrating with first principles calcns., we show that the SSW-RS method can be applied to investigate the kinetics of complex org. reactions featuring many possible reaction channels and complex hydrogen-bonding networks, as demonstrated here using two examples, epoxypropane hydrolysis in aq. soln. and β-D-glucopyranose decompn. Our results show that simultaneous sampling of the soft hydrogen-bonding conformations and the chem. reactions involving hard bond making/breaking can be achieved in the SSW-RS simulation, and the mechanism and kinetics can be predicted without a priori information on the system. Unexpected new chem. for these reactions is revealed and discussed. In particular, despite many possible pathways for β-D-glucopyranose decompn., the SSW-RS shows that only β-D-glucose and levoglucosan are kinetically preferred direct products and the 5- or 7-member ring products should be secondary products derived from β-D-glucose or levoglucosan. As a general tool for reactivity prediction, the SSW-RS opens a new route for the design of rational reactions.
- 61Vázquez, S. A.; Martínez-Núñez, E. HCN Elimination from Vinyl Cyanide: Product Energy Partitioning, the Role of Hydrogen–Deuterium Exchange Reactions and a New Pathway. Phys. Chem. Chem. Phys. 2015, 17, 6948– 6955, DOI: 10.1039/C4CP05626DGoogle Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXit1aquro%253D&md5=7d4dd3daa6fd88d8777f26838c395778HCN elimination from vinyl cyanide: product energy partitioning, the role of hydrogen-deuterium exchange reactions and a new pathwayVazquez, Saulo A.; Martinez-Nunez, EmilioPhysical Chemistry Chemical Physics (2015), 17 (10), 6948-6955CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The different HCN elimination pathways from vinyl cyanide (VCN) are studied in this paper using RRKM, Kinetic Monte Carlo (KMC), and quasi-classical trajectory (QCT) calcns. A new HCN elimination pathway proves to be very competitive with the traditional 3-center and 4-center mechanisms, particularly at low excitation energies. However, low excitation energies have never been exptl. explored, and the high and low excitation regions are dynamically different. The KMC simulations carried out using singly deuterated VCN (CH2=CD-CN) at 148 kcal mol-1 show the importance of hydrogen-deuterium exchange reactions: both DCN and HCN will be produced in any of the 1,1 and 1,2 elimination pathways. The QCT simulation results obtained for the 3-center pathway are in agreement with the available exptl. results, with the 4-center results showing much more excitation of the products. In general, results seem to be consistent with a photodissocn. mechanism at 193 nm, where the mol. dissocs. (at least the HCN elimination pathways) in the ground electronic state. However, simulations assume that internal conversion is a fully statistical process, i.e., the HCN elimination channels proceed on the ground electronic state according to RRKM theory, which might not be the case. In future studies it would be of interest to include the photo-prepd. electronically excited state(s) in the dynamics simulations.
- 62Martínez-Núñez, E. An Automated Method to Find Transition States Using Chemical Dynamics Simulations. J. Comput. Chem. 2015, 36, 222– 234, DOI: 10.1002/jcc.23790Google Scholar62https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGgtLbO&md5=e22946d4913acb912ffd139e36d6c11cAn automated method to find transition states using chemical dynamics simulationsMartinez-Nunez, EmilioJournal of Computational Chemistry (2015), 36 (4), 222-234CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)A procedure to automatically find the transition states (TSs) of a mol. system (MS) is proposed. It has two components: high-energy chem. dynamics simulations (CDS), and an algorithm that analyzes the geometries along the trajectories to find reactive pathways. Two levels of electronic structure calcns. are involved: a low level (LL) is used to integrate the trajectories and also to optimize the TSs, and a higher level (HL) is used to reoptimize the structures. The method has been tested in three MSs: formaldehyde, formic acid (FA), and vinyl cyanide (VC), using MOPAC2012 and Gaussian09 to run the LL and HL calcns., resp. Both the efficacy and efficiency of the method are very good, with around 15 TS structures optimized every 10 trajectories, which gives a total of 7, 12, and 83 TSs for formaldehyde, FA, and VC, resp. The use of CDS makes it a powerful tool to unveil possible nonstatistical behavior of the system under study. © 2014 Wiley Periodicals, Inc.
- 63Martínez-Núñez, E. An Automated Transition State Search Using Classical Trajectories Initialized at Multiple Minima. Phys. Chem. Chem. Phys. 2015, 17, 14912– 14921, DOI: 10.1039/C5CP02175HGoogle Scholar63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnslOqsLo%253D&md5=695f6ea8566cc28afe6bb7c89a434bbeAn automated transition state search using classical trajectories initialized at multiple minimaMartinez-Nunez, EmilioPhysical Chemistry Chemical Physics (2015), 17 (22), 14912-14921CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Very recently, we proposed an automated method for finding transition states of chem. reactions using dynamics simulations; the method has been termed Transition State Search using Chem. Dynamics Simulations (TSSCDS) (E. Martinez-Nunez, J. Comput. Chem., 2015, 36, 222-234). In the present work, an improved automated search procedure is developed, which consists of iteratively running different ensembles of trajectories initialized at different min. The iterative TSSCDS method is applied to the complex C3H4O system, obtaining a total of 66 different min. and 276 transition states. With the obtained transition states and paths, statistical RRKM calcns. and Kinetic Monte Carlo simulations are carried out to study the fragmentation dynamics of propenal, which is the global min. of the system. The kinetic simulations provide a (three-body dissocn.)/(CO elimination) ratio of 1.49 for an excitation energy of 148 kcal mol-1, which agrees well with the corresponding value obtained in the photolysis of propenal at 193 nm (1.1), suggesting that at least these two channels: three-body dissocn. (to give H2 + CO + C2H2) and CO elimination occur on the ground electronic state.
- 64Varela, J. A.; Vázquez, S. A.; Martínez-Núñez, E. An Automated Method to Find Reaction Mechanisms and Solve the Kinetics in Organometallic Catalysis. Chem. Sci. 2017, 8, 3843– 3851, DOI: 10.1039/C7SC00549KGoogle Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjsl2rtr8%253D&md5=df77d0eab3dac5fc42530661b1d57954An automated method to find reaction mechanisms and solve the kinetics in organometallic catalysisVarela, J. A.; Vazquez, S. A.; Martinez-Nunez, E.Chemical Science (2017), 8 (5), 3843-3851CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)A novel computational method is proposed in this work for use in discovering reaction mechanisms and solving the kinetics of transition metal-catalyzed reactions. The method does not rely on either chem.intuition or assumed a priori mechanisms, and it works in a fully automated fashion. Its core is a procedure, recently developed by one of the authors, that combines accelerated direct dynamics with an efficient geometry-based post-processing algorithm to find transition states. In the present work, several auxiliary tools have been added to deal with the specific features of transition metal catalytic reactions. As a test case, we chose the cobalt-catalyzed hydroformylation of ethylene because of its well-established mechanism, and the fact that it has already been used in previous automated computational studies. Besides the generally accepted mechanism of Heck and Breslow, several side reactions, such as hydrogenation of the alkene, emerged from our calcns. Addnl., the calcd.rate law for the hydroformylation reaction agrees reasonably well with those obtained in previous exptl.and theor.studies.
- 65Rodriguez, A.; Rodriguez-Fernandez, R.; Vazquez, S. A.; Barnes, G. L.; Stewart, J. J. P.; Martinez-Nunez, E. tsscds2018: A Code for Automated Discovery of Chemical Reaction Mechanisms and Solving the Kinetics. J. Comput. Chem. 2018, 39, 1922– 1930, DOI: 10.1002/jcc.25370Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhslOksr7J&md5=f0374c367acd28cb3cf2ebedb5ef3eeetsscds2018: A code for automated discovery of chemical reaction mechanisms and solving the kineticsRodriguez, Aurelio; Rodriguez-Fernandez, Roberto; A. Vazquez, Saulo; L. Barnes, George; J. P. Stewart, James; Martinez-Nunez, EmilioJournal of Computational Chemistry (2018), 39 (23), 1922-1930CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)A new software, called tsscds2018, has been developed to discover reaction mechanisms and solve the kinetics in a fully automated fashion. The program employs algorithms based on Graph Theory to find transition state (TS) geometries from accelerated semiempirical dynamics simulations carried out with MOPAC2016. Then, the TSs are connected to the corresponding min. and the reaction network is obtained. Kinetic data like populations vs time or the abundancies of each product can also be obtained with our program thanks to a Kinetic Monte Carlo routine. Highly accurate ab initio potential energy diagrams and kinetics can also be obtained using an interface with Gaussian09. The source code is available on the following site: © 2018 Wiley Periodicals, Inc.
- 66Cerjan, C. J.; Miller, W. H. On Finding Transition States. J. Chem. Phys. 1981, 75, 2800– 2806, DOI: 10.1063/1.442352Google Scholar66https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3MXltlyqsrY%253D&md5=62bc3d736a49a1df81c3f7b428117645On finding transition statesCerjan, Charles J.; Miller, William H.Journal of Chemical Physics (1981), 75 (6), 2800-6CODEN: JCPSA6; ISSN:0021-9606.An algorithm for locating transition states on a potential energy surface is described. The most important feature of the algorithm, which makes explicit use of the second deriv. matrix of the potential surface, is that it is able to "walk uphill" from the min. on a potential surface to the transition state essentially automatically. The method is illustrated by application to a two dimensional model problem, to the vinylidene-acetylene rearrangement (H2C = C:↔HC≡CH), and to the dissocn. and rearrangement of formaldehyde (H2CO↔H2 + O, HCOH). The algorithm is also seen to provide an improved way of following a reaction path from a transition state down to reactants or products.
- 67Simons, J.; Joergensen, P.; Taylor, H.; Ozment, J. Walking on Potential Energy Surfaces. J. Phys. Chem. 1983, 87, 2745– 2753, DOI: 10.1021/j100238a013Google Scholar67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3sXksF2it74%253D&md5=af251d7a8647c328879862fd7cde68a3Walking on potential energy surfacesSimons, Jack; Joergensen, Poul; Taylor, Hugh; Ozment, JudyJournal of Physical Chemistry (1983), 87 (15), 2745-53CODEN: JPCHAX; ISSN:0022-3654.By combining a local quadratic approxn. to the potential energy surface with the concept of a trust radius within which this quadratic approxn. is accurate and a scaling of one active coordinate, an automated surface walking algorithm was developed. This algorithm allows one to walk from geometries characteristic of equil. mol. structures, uphill along stream beds, through transition-state geometries, and onward to product-mol. equil. geometries. The method was appled to model and ab initio test cases with encouraging results. The success of using the algorithm in connection with approx. Hessian matrixes formed via so-called update techniques, which require only local force information, is esp. encouraging in light of the high cost of ab initio anal. evaluation of the Hessian.
- 68Davis, H. L.; Wales, D. J.; Berry, R. S. Exploring Potential Energy Surfaces with Transition State Calculations. J. Chem. Phys. 1990, 92, 4308– 4319, DOI: 10.1063/1.457790Google Scholar68https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3cXit1elu74%253D&md5=c2ae2665bcc5e23802f289641cd94e3cExploring potential energy surfaces with transition state calculationsDavis, Heidi L.; Wales, David J.; Berry, R. StephenJournal of Chemical Physics (1990), 92 (7), 4308-19CODEN: JCPSA6; ISSN:0021-9606.Means are presented for using stationary points in two ways. One, for well-understood potentials, elucidates relations between the form of the surface and the dynamics that it supports, including the detn. of the effective mol. symmetry group. The other, for potentials of uncertain quality, provides a test for unphys. characteristics and suggests how the surface might be improved if it is found to be unsatisfactory in some respect. Our approach involves comparison of transition-state calcns. using the slowest-slide and Cerjan-Miller algorithms for two systems: the Lennard-Jones Ar7 cluster, and the Handy-Carter many-body-expansion potential for the ground state of formaldehyde.
- 69Wales, D. J. Basins of Attraction for Stationary Points on a Potential-Energy Surface. J. Chem. Soc., Faraday Trans. 1992, 88, 653– 657, DOI: 10.1039/ft9928800653
- 70Wales, D. J. Locating Stationary Points for Clusters in Cartesian Coordinates. J. Chem. Soc., Faraday Trans. 1993, 89, 1305– 1313, DOI: 10.1039/ft9938901305Google Scholar70https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXksFKmu78%253D&md5=b823814bb89c8e62b4e904ae2d37b45dLocating stationary points for clusters in cartesian coordinatesWales, David J.Journal of the Chemical Society, Faraday Transactions (1993), 89 (9), 1305-13,4 platesCODEN: JCFTEV; ISSN:0956-5000.Location of min. and transition states on a potential energy surface by the eigenvector-following method using Cartesian coordinates and a projection operator is described. Comparisons with calcns. employing std. internal coordinates are made for a wide variety of model clusters. The new method, suggested by Baker and Hehre (1991), generally produces faster convergence and solves a no. of problems that are inherent when using distance, bond angle, and dihedral angle internal coordinates. In particular, eigenvector-following calcns. using analytic first and second energy derivs. should now be possible for much larger systems. Some example reaction paths are illustrated, including a new facetting rearrangement of 55- and 147-atom Mackay icosahedra. The basins of attraction of min. and transition states are also calcd., i.e., the regions of the potential-energy surface for which stationary-point searches converge to a given structure. The superiority of the projection operator approach is again demonstrated, and the previous observation that initial geometrical contraction is helpful in transition-state searches is confirmed.
- 71Jensen, F. Locating Transition Structures by Mode Following: A Comparison of Six Methods on the Ar8Lennard-Jones Potential. J. Chem. Phys. 1995, 102, 6706– 6718, DOI: 10.1063/1.469144
- 72Doye, J. P. K.; Wales, D. J. Surveying a Potential Energy Surface by Eigenvector-Following. Z. Phys. D: At., Mol. Clusters 1997, 40, 194– 197, DOI: 10.1007/s004600050192Google Scholar72https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXjs12rtrw%253D&md5=affb326a8ca9636d1e24e1b5937b840eSurveying a potential energy surface by eigenvector-following. Applications to global optimization and the structural transformations of clustersDoye, J. P. K.; Wales, D. J.Zeitschrift fuer Physik D: Atoms, Molecules and Clusters (1997), 40 (1-4), 194-197CODEN: ZDACE2; ISSN:0178-7683. (Springer)We have developed a method to search potential energy surfaces which avoids some of the difficulties assocd. with trapping in local min. Steps are directly taken between min. using eigenvector-following. Exploration of this space by low temp. Metropolis Monte Carlo is a useful global optimization tool. This method successfully finds the lowest energy icosahedral min. of Lennard-Jones clusters from random starting configurations, but cannot find the global min. in a reasonable time for difficult cases such as the 38-atom Lennard-Jones cluster where the face-centered-cubic truncated octahedron is lowest in energy. However, by performing searches at higher temps., we have found a pathway between the truncated octahedron and the lowest energy icosahedral min. Such a pathway may be illustrative of some of the structural transformations that are obsd. for supported metal clusters by electron microscopy.
- 73Broyden, C. G. Quasi-Newton Methods and Their Application to Function Minimisation. Math. Comp. 1967, 21, 368– 381, DOI: 10.1090/S0025-5718-1967-0224273-2
- 74Munro, L. J.; Wales, D. J. Defect Migration in Crystalline Silicon. Phys. Rev. B: Condens. Matter Mater. Phys. 1999, 59, 3969– 3980, DOI: 10.1103/PhysRevB.59.3969Google Scholar74https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXosVeltw%253D%253D&md5=a958a13eef54db0261a60a64d4e77e87Defect migration in crystalline siliconMunro, Lindsey J.; Wales, David J.Physical Review B: Condensed Matter and Materials Physics (1999), 59 (6), 3969-3980CODEN: PRBMDO; ISSN:0163-1829. (American Physical Society)A no. of vacancy and interstitial defect migration mechanisms were characterized for cryst. Si using supercells contg. 64 and 216 atoms and a tight-binding approach. The authors study various defect configurations corresponding to min. and the pathways that connect them. A modified eigenvector-following approach was used to locate true transition states. The authors exploit the fact that only one Hessian eigenvector is needed to define the uphill search direction and use conjugate gradient minimization in the tangent space to produce a hybrid algorithm. Two implementations of this approach are considered, the 1st where 2nd derivs. are available but full diagonalization of the Hessian would be the most time-consuming step, and the 2nd where only 1st derivs. of the energy are known.
- 75Malek, R.; Mousseau, N. Dynamics of Lennard-Jones Clusters: A Characterization of the Activation-Relaxation Technique. Phys. Rev. E: Stat. Phys., Plasmas, Fluids, Relat. Interdiscip. Top. 2000, 62, 7723– 7728, DOI: 10.1103/PhysRevE.62.7723Google Scholar75https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXoslahurw%253D&md5=73391e2c5502b4312a8cdd0f07852b91Dynamics of Lennard-Jones clusters: A characterization of the activation-relaxation techniqueMalek, Rachid; Mousseau, NormandPhysical Review E: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics (2000), 62 (6-A), 7723-7728CODEN: PLEEE8; ISSN:1063-651X. (American Physical Society)The potential energy surface of Lennard-Jones clusters is investigated using the activation-relaxation technique (ART). This method defines events in the configurational energy landscape as a two-step process: (a) a configuration is first activated from a local min. to a nearby saddle-point, and (b) is then relaxed to a new min. Although ART has been applied with success to a wide range of materials such as a-Si, a-SiO2, and binary Lennard-Jones glasses, questions remain regarding the biases of the technique. We address some of these questions in a detailed study of ART-generated events in Lennard-Jones clusters, a system for which much is already known. In particular, we study the distribution of saddle-points, the pathways between configurations, and the reversibility of paths. We find that ART can identify all trajectories with a first-order saddle point leaving a given min., is fully reversible, and samples events following the Boltzmann wt. at the saddle point.
- 76Deglmann, P.; Furche, F. Efficient Characterization of Stationary Points on Potential Energy Surfaces. J. Chem. Phys. 2002, 117, 9535– 9538, DOI: 10.1063/1.1523393Google Scholar76https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XovVSru78%253D&md5=3bbd5b3b826d7210588dbb7121b72176Efficient characterization of stationary points on potential energy surfacesDeglmann, Peter; Furche, FilippJournal of Chemical Physics (2002), 117 (21), 9535-9538CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Traditional methods for characterizing an optimized mol. structure as a min. or as a saddle point on the nuclear potential energy surface require the full Hessian. However, if f denotes the no. of nuclear degrees of freedom, a full Hessian calcn. is more expensive than a single point geometry optimization step by the order of magnitude of f. Here we present a method which allows to det. the lowest vibrational frequencies of a mol. at significantly lower cost. Our approach takes advantage of the fact that only a few perturbed first-order wave functions need to be computed in an iterative diagonalization scheme instead of f ones in a full Hessian calcn. We outline an implementation for Hartree-Fock and d. functional methods. Applications indicate a scaling similar to that of a single point energy or gradient calcn., but with a larger prefactor. Depending on the no. of soft vibrational modes, the iterative method becomes effective for systems with more than 30-50 atoms.
- 77Reiher, M.; Neugebauer, J. A Mode-Selective Quantum Chemical Method for Tracking Molecular Vibrations Applied to Functionalized Carbon Nanotubes. J. Chem. Phys. 2003, 118, 1634– 1641, DOI: 10.1063/1.1523908Google Scholar77https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjtVaquw%253D%253D&md5=616ea82fd0a616e1c7c6428c4581da7bA mode-selective quantum chemical method for tracking molecular vibrations applied to functionalized carbon nanotubesReiher, Markus; Neugebauer, JohannesJournal of Chemical Physics (2003), 118 (4), 1634-1641CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The theor. investigation of mesoscopic objects requires new techniques which are particularly suited for the study of selected aspects of these systems. Vibrational spectroscopy is a main source for structural information on heterogeneous systems. We present an efficient quantum chem. method, which relies on a modified Davidson algorithm for targeting selected vibrations in IR and Raman spectra. This approach is applied to the characteristic breathing modes of single-walled carbon nanotubes.
- 78Sharada, S. M.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Automated Transition State Searches without Evaluating the Hessian. J. Chem. Theory Comput. 2012, 8, 5166– 5174, DOI: 10.1021/ct300659d
- 79Bergeler, M.; Herrmann, C.; Reiher, M. Mode-Tracking Based Stationary-Point Optimization. J. Comput. Chem. 2015, 36, 1429– 1438, DOI: 10.1002/jcc.23958Google Scholar79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXpvFWgt7c%253D&md5=50ae502b58d1b2eb8f04225407e085afMode-tracking based stationary-point optimizationBergeler, Maike; Herrmann, Carmen; Reiher, MarkusJournal of Computational Chemistry (2015), 36 (19), 1429-1438CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)In this work, we present a transition-state optimization protocol based on the Mode-Tracking algorithm [Reiher and Neugebauer, J. Chem. Phys., 2003, 118, 1634]. By calcg. only the eigenvector of interest instead of diagonalizing the full Hessian matrix and performing an eigenvector following search based on the selectively calcd. vector, we can efficiently optimize transition-state structures. The initial guess structures and eigenvectors are either chosen from a linear interpolation between the reactant and product structures, from a nudged-elastic band search, from a constrained-optimization scan, or from the min.-energy structures. Alternatively, initial guess vectors based on chem. intuition may be defined. We then iteratively refine the selected vectors by the Davidson subspace iteration technique. This procedure accelerates finding transition states for large mols. of a few hundred atoms. It is also beneficial in cases where the starting structure is very different from the transition-state structure or where the desired vector to follow is not the one with lowest eigenvalue. Explorative studies of reaction pathways are feasible by following manually constructed mol. distortions. © 2015 Wiley Periodicals, Inc.
- 80Halgren, T. A.; Lipscomb, W. N. The Synchronous-Transit Method for Determining Reaction Pathways and Locating Molecular Transition States. Chem. Phys. Lett. 1977, 49, 225– 232, DOI: 10.1016/0009-2614(77)80574-5Google Scholar80https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE2sXlsFWmtLs%253D&md5=90c0d95b096220fddcc7eebc0639fdfdThe synchronous-transit method for determining reaction pathways and locating molecular transition statesHalgren, Thomas A.; Lipscomb, William N.Chemical Physics Letters (1977), 49 (2), 225-32CODEN: CHPLBC; ISSN:0009-2614.In the synchronous-transit method, a model linear synchronous transit pathway is first constructed and is then refined by optimizing 1 or more intermediate structures subject to the constraint that the optimized structure retain the same relative position along the path orthogonal optimization. The method yields a series of energy ests. which progressively bound the energy of the transition state from above and from below. High computational efficiency is attainable, and sufficient flexibility is provided to deal with asynchronous processes. Comparisons are made to the alternative reaction-coordinate approach. The method is applied to a model 2-dimensional energy surface and to the allowed electrocyclic interconversions of the cyclopropyl and allyl cations and of cyclobutene and cis-butadiene.
- 81Ayala, P. Y.; Schlegel, H. B. A Combined Method for Determining Reaction Paths, Minima, and Transition State Geometries. J. Chem. Phys. 1997, 107, 375– 384, DOI: 10.1063/1.474398Google Scholar81https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXksVeksrY%253D&md5=2ec17a4bf9a0f0f848e6fe0b844fe250A combined method for determining reaction paths, minima, and transition state geometriesAyala, Philippe Y.; Schlegel, H. BernhardJournal of Chemical Physics (1997), 107 (2), 375-384CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Mapping out a reaction mechanism involves optimizing the reactants and products, finding the transition state and following the reaction path connecting them. Transition states can be difficult to locate and reaction paths can be expensive to follow. We describe an efficient algorithm for detg. the transition state, min. and reaction path in a single procedure. Starting with an approx. path represented by N points, the path is iteratively relaxed until one of the N points reached the transition state, the end points optimize to min. and the remaining points converged to a second order approxn. of the steepest descent path. The method appears to be more reliable than conventional transition state optimization algorithms, and requires only energies and gradients, but not second deriv. calcns. The procedure is illustrated by application to a no. of model reactions. In most cases, the reaction mechanism can be described well using 5 to 7 points to represent the transition state, the min. and the path. The computational cost of relaxing the path is less than or comparable to the cost of std. techniques for finding the transition state and the min., detg. the transition vector and following the reaction path on both sides of the transition state.
- 82Henkelman, G.; Jónsson, H. A Dimer Method for Finding Saddle Points on High Dimensional Potential Surfaces Using Only First Derivatives. J. Chem. Phys. 1999, 111, 7010– 7022, DOI: 10.1063/1.480097Google Scholar82https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXmt1Ojurc%253D&md5=d3628bc9e56615b91730dd2224a36723A dimer method for finding saddle points on high dimensional potential surfaces using only first derivativesHenkelman, Graeme; Jonsson, HannesJournal of Chemical Physics (1999), 111 (15), 7010-7022CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The problem of detg. which activated (and slow) transitions can occur from a given initial state at a finite temp. is addressed. In the harmonic approxn. to transition state theory this problem reduces to finding the set of low lying saddle points at the boundary of the potential energy basin assocd. with the initial state, as well as the relevant vibrational frequencies. Also, when full transition state theory calcns. are carried out, it can be useful to know the location of the saddle points on the potential energy surface. A method for finding saddle points without knowledge of the final state of the transition is described. The method only makes use of first derivs. of the potential energy and is, therefore, applicable in situations where second derivs. are too costly or too tedious to evaluate, for example, in plane wave based d. functional theory calcns. It is also designed to scale efficiently with the dimensionality of the system and can be applied to very large systems when empirical or semiempirical methods are used to obtain the at. forces. The method can be started from the potential min. representing the initial state, or from an initial guess closer to the saddle point. An application to Al adatom diffusion on an Al(100) surface described by an embedded atom method potential is presented. A large no. of saddle points were found for adatom diffusion and dimer/vacancy formation. A surprisingly low energy four atom exchange process was found as well as processes indicative of local hex reconstruction of the surface layer.
- 83Henkelman, G.; Uberuaga, B. P.; Jónsson, H. A Climbing Image Nudged Elastic Band Method for Finding Saddle Points and Minimum Energy Paths. J. Chem. Phys. 2000, 113, 9901– 9904, DOI: 10.1063/1.1329672Google Scholar83https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFagurc%253D&md5=3899b9e2e9e3eb74009987d96623f018A climbing image nudged elastic band method for finding saddle points and minimum energy pathsHenkelman, Graeme; Uberuaga, Blas P.; Jonsson, HannesJournal of Chemical Physics (2000), 113 (22), 9901-9904CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)A modification of the nudged elastic band method for finding min. energy paths is presented. One of the images is made to climb up along the elastic band to converge rigorously on the highest saddle point. Also, variable spring consts. are used to increase the d. of images near the top of the energy barrier to get an improved est. of the reaction coordinate near the saddle point. Applications to CH4 dissociative adsorption on Ir(111) and H2 on Si(100) using plane wave based d. functional theory are presented.
- 84Henkelman, G.; Jónsson, H. Improved Tangent Estimate in the Nudged Elastic Band Method for Finding Minimum Energy Paths and Saddle Points. J. Chem. Phys. 2000, 113, 9978– 9985, DOI: 10.1063/1.1323224Google Scholar84https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFagu7Y%253D&md5=57dbeadabf6061460912090f40b581e0Improved tangent estimate in the nudged elastic band method for finding minimum energy paths and saddle pointsHenkelman, Graeme; Jonsson, HannesJournal of Chemical Physics (2000), 113 (22), 9978-9985CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)An improved way of estg. the local tangent in the nudged elastic band method for finding min. energy paths is presented. In systems where the force along the min. energy path is large compared to the restoring force perpendicular to the path and when many images of the system are included in the elastic band, kinks can develop and prevent the band from converging to the min. energy path. We show how the kinks arise and present an improved way of estg. the local tangent which solves the problem. The task of finding an accurate energy and configuration for the saddle point is also discussed and examples given where a complementary method, the dimer method, is used to efficiently converge to the saddle point. Both methods only require the first deriv. of the energy and can, therefore, easily be applied in plane wave based d.-functional theory calcns. Examples are given from studies of the exchange diffusion mechanism in a Si crystal, Al addimer formation on the Al(100) surface, and dissociative adsorption of CH4 on an Ir(111) surface.
- 85Maragakis, P.; Andreev, S. A.; Brumer, Y.; Reichman, D. R.; Kaxiras, E. Adaptive Nudged Elastic Band Approach for Transition State Calculation. J. Chem. Phys. 2002, 117, 4651– 4658, DOI: 10.1063/1.1495401Google Scholar85https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmsVWntbo%253D&md5=9645dcee50aacfef2aa9265a1989ac1eAdaptive nudged elastic band approach for transition state calculationMaragakis, P.; Andreev, Stefan A.; Brumer, Yisroel; Reichman, David R.; Kaxiras, EfthimiosJournal of Chemical Physics (2002), 117 (10), 4651-4658CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)We present a method for the location of transition states in complicated phys. systems. Our algorithm is a variation of the well-established nudged elastic band method and leads to significant improvements in efficiency and accuracy. We assess the applicability of our method by testing it on several systems of practical interest representing a variety of phys. situations. At the mol. level, we apply the method to tautomerization processes in nucleic acid bases and the double proton transfer in nucleic acid base pairs. For bulk systems, we considered the concerted exchange mechanism in Si, which is a complicated pathway for defect-free diffusion in the diamond lattice. For surface systems, we considered ad-dimer diffusion mechanisms on Si(100). We incorporated the climbing image extension of the nudged elastic band method and compared it against the original approach on two-dimensional model potential energy surfaces. Based on favorable comparisons with related methods and the general implementation of our method, we believe that this is well suited for efficient ests. of activation barriers with sophisticated electronic structure codes.
- 86E, W.; Ren, W.; Vanden-Eijnden, E. String Method for the Study of Rare Events. Phys. Rev. B: Condens. Matter Mater. Phys. 2002, 66, 052301, DOI: 10.1103/PhysRevB.66.052301Google Scholar86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmvVSlurg%253D&md5=1c24a86bf403c333e9705f00876e4aa3String method for the study of rare eventsE, Weinan; Ren, Weiqing; Vanden-Eijnden, EricPhysical Review B: Condensed Matter and Materials Physics (2002), 66 (5), 052301/1-052301/4CODEN: PRBMDO; ISSN:0163-1829. (American Physical Society)We present an efficient method for computing the transition pathways, free energy barriers, and transition rates in complex systems with relatively smooth energy landscapes. The method proceeds by evolving strings, i.e., smooth curves with intrinsic parametrization whose dynamics takes them to the most probable transition path between two metastable regions in configuration space. Free energy barriers and transition rates can then be detd. by a std. umbrella sampling around the string. Applications to Lennard-Jones cluster rearrangement and thermally induced switching of a magnetic film are presented.
- 87E, W.; Ren, W.; Vanden-Eijnden, E. Finite Temperature String Method for the Study of Rare Events. J. Phys. Chem. B 2005, 109, 6688– 6693, DOI: 10.1021/jp0455430Google Scholar87https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtFSnsbo%253D&md5=f92a743d5d4b946756c04c6c1cbc8a8dFinite Temperature String Method for the Study of Rare EventsE, Weinan; Ren, Weiqing; Vanden-Eijnden, EricJournal of Physical Chemistry B (2005), 109 (14), 6688-6693CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)A method is presented for the study of rare events such as conformational changes arising in activated processes whose reaction coordinate is not known beforehand and for which the assumptions of transition state theory are invalid. The method samples the energy landscape adaptively and dets. the isoprobability surfaces for the transition: by definition the trajectories initiated anywhere on one of these surfaces has equal probability to reach first one metastable set rather than the other. Upon weighting these surfaces by the equil. probability distribution, one obtains an effective transition pathway, i.e., a tube in configuration space inside which conformational changes occur with high probability, and the assocd. rate. The method is first validated on a simple two-dimensional example; then it is applied to a model of solid-solid transformation of a condensed system.
- 88Behn, A.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Efficient Exploration of Reaction Paths via a Freezing String Method. J. Chem. Phys. 2011, 135, 224108, DOI: 10.1063/1.3664901Google Scholar88https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1SkurrN&md5=01c0f45d3455f92d1341022377717530Efficient exploration of reaction paths via a freezing string methodBehn, Andrew; Zimmerman, Paul M.; Bell, Alexis T.; Head-Gordon, MartinJournal of Chemical Physics (2011), 135 (22), 224108/1-224108/9CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The ability to efficiently locate transition states is critically important to the widespread adoption of theor. chem. techniques for their ability to accurately predict kinetic consts. Existing surface walking techniques to locate such transition states typically require an extremely good initial guess that is often beyond intuition to est. To alleviate this problem, automated techniques to locate transition state guesses have been created that take the known reactant and product endpoint structures as inputs. In this work, we present a simple method to build an approx. reaction path through a combination of interpolation and optimization. Starting from the known reactant and product structures, new nodes are interpolated inwards towards the transition state, partially optimized orthogonally to the reaction path, and then frozen before a new pair of nodes is added. The algorithm is stopped once the string ends connect. For the practical user, this method provides a quick and convenient way to generate transition state structure guesses. Tests on three reactions (cyclization of cis,cis-2,4-hexadiene, alanine dipeptide conformation transition, and ethylene dimerization in a Ni-exchanged zeolite) show that this "freezing string" method is an efficient way to identify complex transition states with significant cost savings over existing methods, particularly when high quality linear synchronous transit interpolation is employed. (c) 2011 American Institute of Physics.
- 89Behn, A.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Incorporating Linear Synchronous Transit Interpolation into the Growing String Method: Algorithm and Applications. J. Chem. Theory Comput. 2011, 7, 4019– 4025, DOI: 10.1021/ct200654uGoogle Scholar89https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOqurjE&md5=f76c6427d713c0375114e0262ef0d29eIncorporating Linear Synchronous Transit Interpolation into the Growing String Method: Algorithm and ApplicationsBehn, Andrew; Zimmerman, Paul M.; Bell, Alexis T.; Head-Gordon, MartinJournal of Chemical Theory and Computation (2011), 7 (12), 4019-4025CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The growing string method is a powerful tool in the systematic study of chem. reactions with theor. methods which allows for the rapid identification of transition states connecting known reactant and product structures. However, the efficiency of this method is heavily influenced by the choice of interpolation scheme when adding new nodes to the string during optimization. In particular, the use of Cartesian coordinates with cubic spline interpolation often produces guess structures which are far from the final reaction path and require many optimization steps (and thus many energy and gradient calcns.) to yield a reasonable final structure. In this paper, we present a new method for interpolating and reparameterizing nodes within the growing string method using the linear synchronous transit method of Halgren and Lipscomb. When applied to the alanine dipeptide rearrangement and a simplified cationic alkyl ring condensation reaction, a significant speedup in terms of computational cost is achieved (30-50%).
- 90Zimmerman, P. Reliable Transition State Searches Integrated with the Growing String Method. J. Chem. Theory Comput. 2013, 9, 3043– 3050, DOI: 10.1021/ct400319wGoogle Scholar90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXptFeht78%253D&md5=6f5715237172541a74de71a1781cee83Reliable Transition State Searches Integrated with the Growing String MethodZimmerman, PaulJournal of Chemical Theory and Computation (2013), 9 (7), 3043-3050CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The growing string method (GSM) is highly useful for locating reaction paths connecting two mol. intermediates. GSM has often been used in a two-step procedure to locate exact transition states (TS), where GSM creates a quality initial structure for a local TS search. This procedure and others like it, however, do not always converge to the desired transition state because the local search is sensitive to the quality of the initial guess. This article describes an integrated technique for simultaneous reaction path and exact transition state search. This is achieved by implementing an eigenvector following optimization algorithm in internal coordinates with Hessian update techniques. After partial convergence of the string, an exact saddle point search begins under the constraint that the maximized eigenmode of the TS node Hessian has significant overlap with the string tangent near the TS. Subsequent optimization maintains connectivity of the string to the TS as well as locks in the TS direction, all but eliminating the possibility that the local search leads to the wrong TS. To verify the robustness of this approach, reaction paths and TSs are found for a benchmark set of more than 100 elementary reactions.
- 91Vaucher, A. C.; Reiher, M. Minimum Energy Paths and Transition States by Curve Optimization. J. Chem. Theory Comput. 2018, 14, 3091– 3099, DOI: 10.1021/acs.jctc.8b00169Google Scholar91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXnsF2qtbg%253D&md5=88c0d81d005d0b913d9b75341576889dMinimum Energy Paths and Transition States by Curve OptimizationVaucher, Alain C.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (6), 3091-3099CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Transition states and min. energy paths are essential to understand and predict chem. reactivity. Double-ended methods represent a std. approach for their detn. A new double-ended method that optimizes reaction paths described by curves is introduced. Unlike other methods, the approach optimizes the curve parameters rather than distinct structures along the path. With mol. paths represented as continuous curves, the optimization can benefit from the advantages of an integral-based formulation. This approach is called ReaDuct and its applicability for mol. paths parametrized by B-spline curves is demonstrated.
- 92Broadbelt, L. J.; Stark, S. M.; Klein, M. T. Computer Generated Pyrolysis Modeling: On-the-Fly Generation of Species, Reactions, and Rates. Ind. Eng. Chem. Res. 1994, 33, 790– 799, DOI: 10.1021/ie00028a003Google Scholar92https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXitFKnu7s%253D&md5=7cfd4d0b5f978bbea1c40e00eadcbf77Computer Generated Pyrolysis Modeling: On-the-Fly Generation of Species, Reactions, and RatesBroadbelt, Linda J.; Stark, Scott M.; Klein, Michael T.Industrial & Engineering Chemistry Research (1994), 33 (4), 790-9CODEN: IECRED; ISSN:0888-5885.The development of an integrated system for the computer generation of kinetic models is described. Required input is the structure of the reactants, the reaction rules, and the parameters of a structure/property kinetics correlation. The algorithm transforms this information into reactant/product relationships, i.e., the reaction network, species properties, rate consts., and the FORTRAN code corresponding to the governing species' balance equations, and offers a soln. capability. Graph theory is exploited to represent the constituent atoms of a mol. to allow detn. of species' uniqueness, implement chem. reactions, and identify reaction products. Special attention was devoted to improved algorithm efficiencies, the handling of ring systems, and "on-the-fly" quantum chem. calcns. This general approach is described in using ethane and cyclohexane pyrolysis case studies. The increase in the no. of equations and no. of components for ethane pyrolysis was exponential with the carbon no. of allowed species.
- 93Broadbelt, L. J.; Stark, S. M.; Klein, M. T. Computer Generated Reaction Modelling: Decomposition and Encoding Algorithms for Determining Species Uniqueness. Comput. Chem. Eng. 1996, 20, 113– 129, DOI: 10.1016/0098-1354(94)00009-DGoogle Scholar93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXps1yjsL0%253D&md5=12e4ffb130284518319665befc664e09Computer generated reaction modeling: decomposition and encoding algorithms for determining species uniquenessBroadbelt, L. J.; Stark, S. M.; Klein, M. T.Computers & Chemical Engineering (1996), 20 (2), 113-29CODEN: CCENDW; ISSN:0098-1354. (Elsevier)The concept of computer generated reaction modeling was broadened through the development of a general planar graph algorithm for detn. of isomorphism. The previous capability was limited by its inability to det. the uniqueness of ring-contg. species unambiguously, restricting the application of automatic network generation to non-cyclic species or cyclic species where the ring was not involved in the chem. transformation. In this work, the systematic identification of both noncyclic and cyclic species was carried out by constructing the structurally explicit decompn. tree, an assembly of the biconnected components of the graph, from which a graph invariant unique string code was obtained by iteratively encoding and ordering the subtrees of the decompn. tree. A lexicog. comparison of the unique string code of the candidate species with the string codes of all previously generated species with the same empirical formula allowed unambiguous detn. of species uniqueness.
- 94Broadbelt, L. J.; Pfaendtner, J. Lexicography of Kinetic Modeling of Complex Reaction Networks. AIChE J. 2005, 51, 2112– 2121, DOI: 10.1002/aic.10599Google Scholar94https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslCnt7c%253D&md5=47e8076ea9b3fde03f4c063e018a1131Lexicography of kinetic modeling of complex reaction networksBroadbelt, Linda J.; Pfaendtner, JimAIChE Journal (2005), 51 (8), 2112-2121CODEN: AICEAC; ISSN:0001-1541. (John Wiley & Sons, Inc.)Lexicog. of kinetic modeling of complex reaction networks is discussed.
- 95Evans, M. G.; Polanyi, M. Inertia and Driving Force of Chemical Reactions. Trans. Faraday Soc. 1938, 34, 11– 24, DOI: 10.1039/tf9383400011Google Scholar95https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaA1cXitVWisg%253D%253D&md5=1b35420fa6bfc7cd2c1118fb7a7096ebInertia and driving force of chemical reactionsEvans, M. G.; Polanyi, M.Transactions of the Faraday Society (1938), 34 (), 11-24CODEN: TFSOA4; ISSN:0014-7672.A reaction has "inertia" if the activation energy is exothermic and has a "driving force" when the formation of new bonds lowers the activation energy. The energy surfaces of the initial and final states and the reaction paths between them as well as their relation to at. repulsions are considered.
- 96Matheu, D. M.; Dean, A. M.; Grenda, J. M.; Green, W. H. Mechanism Generation with Integrated Pressure Dependence: A New Model for Methane Pyrolysis. J. Phys. Chem. A 2003, 107, 8552– 8565, DOI: 10.1021/jp0345957Google Scholar96https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXnsVehtLk%253D&md5=087a6a72c1556f599dbf81547530cddeMechanism Generation with Integrated Pressure Dependence: A New Model for Methane PyrolysisMatheu, David M.; Dean, Anthony M.; Grenda, Jeffrey M.; Green, William H., Jr.Journal of Physical Chemistry A (2003), 107 (41), 8552-8565CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Autocatalytic, lower-temp. (≤1100 K) methane pyrolysis has defied mechanistic explanation for almost three decades. The most recent attempt (by Dean in 1990) invoked the chem. activated addn. of an allyl radical to acetylene, leading to a cyclopentadiene/cyclopentadienyl chain-branching system that prompted the obsd. autocatalysis. However, newer, more accurate thermochem. data for the cyclopentadienyl radical render that explanation untenable. A new model for methane pyrolysis is constructed here, using a novel mechanism generation approach that automatically computes any needed rate consts. k(T,P) for chem. or thermally activated pressure-dependent reactions. The computer-generated mechanism accurately predicts the obsd. autocatalysis and concn. profiles without any adjustable parameters. Radical-forming reverse disproportionation reactions-which involve propyne, allene, and fulvene-account for at least half of the exptl. obsd. autocatalytic effect. Many of these reverse disproportionations were neglected in previous studies. The cyclopentadienyl radical is also important, but it is formed primarily by the chem. activated reaction of propargyl with acetylene. New rate ests. for unimol. ring-closure reactions of unsatd. radicals are also presented. This approach is the first to incorporate pressure-dependent reactions generally and systematically during computerized mechanism construction. It successfully identifies complex but crit. chem.-reaction pathways and autocatalytic loops missed by experienced kineticists.
- 97Gao, C. W.; Allen, J. W.; Green, W. H.; West, R. H. Reaction Mechanism Generator: Automatic Construction of Chemical Kinetic Mechanisms. Comput. Phys. Commun. 2016, 203, 212– 225, DOI: 10.1016/j.cpc.2016.02.013Google Scholar97https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xjs12kur4%253D&md5=3403c82513d617761ce38eb7de35c5c3Reaction Mechanism Generator: Automatic construction of chemical kinetic mechanismsGao, Connie W.; Allen, Joshua W.; Green, William H.; West, Richard H.Computer Physics Communications (2016), 203 (), 212-225CODEN: CPHCBZ; ISSN:0010-4655. (Elsevier B.V.)Reaction Mechanism Generator (RMG) constructs kinetic models composed of elementary chem. reaction steps using a general understanding of how mols. react. Species thermochem. is estd. through Benson group additivity and reaction rate coeffs. are estd. using a database of known rate rules and reaction templates. At its core, RMG relies on two fundamental data structures: graphs and trees. Graphs are used to represent chem. structures, and trees are used to represent thermodn. and kinetic data. Models are generated using a rate-based algorithm which excludes species from the model based on reaction fluxes. RMG can generate reaction mechanisms for species involving carbon, hydrogen, oxygen, sulfur, and nitrogen. It also has capabilities for estg. transport and solvation properties, and it automatically computes pressure-dependent rate coeffs. and identifies chem.-activated reaction paths. RMG is an object-oriented program written in Python, which provides a stable, robust programming architecture for developing an extensible and modular code base with a large suite of unit tests. Computationally intensive functions are cythonized for speed improvements.
- 98Harper, M. R.; Van Geem, K. M.; Pyl, S. P.; Marin, G. B.; Green, W. H. Comprehensive Reaction Mechanism for N-Butanol Pyrolysis and Combustion. Combust. Flame 2011, 158, 16– 41, DOI: 10.1016/j.combustflame.2010.06.002Google Scholar98https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVWht7zI&md5=73235ccdbc0fdce97f3c1a8b423bc3bbComprehensive reaction mechanism for n-butanol pyrolysis and combustionHarper, Michael R.; Van Geem, Kevin M.; Pyl, Steven P.; Marin, Guy B.; Green, William H.Combustion and Flame (2011), 158 (1), 16-41CODEN: CBFMAO; ISSN:0010-2180. (Elsevier B.V.)A detailed reaction mechanism for n-butanol, consisting of 263 species and 3381 reactions, has been generated using the open-source software package, Reaction Mechanism Generator (RMG). The mechanism is tested against recently published data - jet-stirred reactor mole fraction profiles, opposed-flow diffusion flame mole fraction profiles, autoignition delay times, and doped methane diffusion flame mole fraction profiles - and newly acquired n-butanol pyrolysis expts. with very encouraging results. The chem. of butanal is also validated against autoignition delay times obtained in shock tube expts. A flux and sensitivity anal. for each simulated dataset is discussed and reveals important reactions where more accurate rate const. ests. were required. New rate const. expressions were computed using quantum chem. and transition state theory calcns. Furthermore, in addn. to comparing the proposed model with the eight datasets, the model is also compared with recently published n-butanol models for three of the datasets. Key differences between the proposed model and the published models are discussed.
- 99van Geem, K. M.; Reyniers, M.-F.; Marin, G. B.; Song, J.; Green, W. H.; Matheu, D. M. Automatic Reaction Network Generation Using RMG for Steam Cracking of N-hexane. AIChE J. 2006, 52, 718– 730, DOI: 10.1002/aic.10655Google Scholar99https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xht1Ogu7s%253D&md5=d20f9949dd0516d2ef7b2bba4d919fa5Automatic reaction network generation using RMG for steam cracking of n-hexaneVan Geem, Kevin M.; Reyniers, Marie-Francoise; Marin, Guy B.; Song, Jing; Green, William H.; Matheu, David M.AIChE Journal (2006), 52 (2), 718-730CODEN: AICEAC; ISSN:0001-1541. (John Wiley & Sons, Inc.)A new reaction mechanism generator RMG is used to automatically construct a pressure dependent kinetic model for the steam cracking of n-hexane. Comparison between simulated and pilot plant data shows that RMG is able to generate detailed reaction networks that accurately predict the conversion and the yields of the major products although none of the kinetic parameters are fit to the expts. RMG generates reaction networks based on minimal assumptions, making it possible to test commonly used assumptions such as the μ-hypothesis and the quasi steady-state approxn. (QSSA) for μ-radicals, traditionally used in steam cracking,1,2 as well as in pyrolysis. The RMG-reaction network for n-hexane confirms that no bimol. reactions of heavy radical species are important at the examd. conditions (COT: 953 K - 1090 K; COP: 0.20 MPa -0.24 MPa; <80% conversion), and that the QSSA for the group of μ-radicals leads to negligible errors. RMG also offers the possibility to est. the error introduced by neglecting the pressure dependence of most of the reactions. In the case studied, this frequently made (but seldom tested) approxn. appears to be justified.
- 100Petway, S. V.; Ismail, H.; Green, W. H.; Estupiñán, E. G.; Jusinski, L. E.; Taatjes, C. A. Measurements and Automated Mechanism Generation Modeling of OH Production in Photolytically Initiated Oxidation of the Neopentyl Radical. J. Phys. Chem. A 2007, 111, 3891– 3900, DOI: 10.1021/jp0668549Google Scholar100https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXkt1Ortrk%253D&md5=65ea9d850eea1b016f8f57d241479b04Measurements and Automated Mechanism Generation Modeling of OH Production in Photolytically Initiated Oxidation of the Neopentyl RadicalPetway, Sarah V.; Ismail, Huzeifa; Green, William H.; Estupinan, Edgar G.; Jusinski, Leonard E.; Taatjes, Craig A.Journal of Physical Chemistry A (2007), 111 (19), 3891-3900CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Prodn. of OH in the reaction of the neopentyl radical with O2 has been measured by a laser photolysis/cw absorption method for various pressures and oxygen concns. at 673, 700, and 725 K. The MIT Reaction Mechanism Generator (RMG) was used to automatically generate a model for this system, and the predicted OH concn. profiles are compared to present and literature exptl. results. Several reactions significantly affect the OH profile. The exptl. data provide useful constraints on the rate coeff. for the formally direct chem. activation reaction of neopentyl radical with O2 to form OH (CH3)3CCH2 + O2 → OH + 3,3-dimethyloxetane (Rxn 1) At 673 K and 60 Torr, log k1 (cm3 mol.-1 s-1) = -13.7 ± 0.5. Abs. absorbance measurements on OH and I indicate that the branching ratio for R + O2 to OH is about 0.03 under these conditions. The data suggest that the ab initio neopentyl + O2 potential energy surface of Sun and Bozzelli is accurate to within 2 kcal mol-1.
- 101Hansen, N.; Merchant, S. S.; Harper, M. R.; Green, W. H. The Predictive Capability of an Automatically Generated Combustion Chemistry Mechanism: Chemical Structures of Premixed Iso-Butanol Flames. Combust. Flame 2013, 160, 2343– 2351, DOI: 10.1016/j.combustflame.2013.05.013Google Scholar101https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXpsV2ksbY%253D&md5=e7e16e09c9c3b50328ce0686d91b3b37The predictive capability of an automatically generated combustion chemistry mechanism: Chemical structures of premixed iso-butanol flamesHansen, Nils; Merchant, Shamel S.; Harper, Michael R.; Green, William H.Combustion and Flame (2013), 160 (11), 2343-2351CODEN: CBFMAO; ISSN:0010-2180. (Elsevier B.V.)The chem. compns. of four low-pressure premixed flames of iso-butanol are investigated with an emphasis on assessing the predictive capabilities of an automatically generated combustion chem. model. This kinetic model had been extensively tested against earlier exptl. data [S.S. Merchant, E.F. Zanoelo, R.L. Speth, M.R. Harper, K.M. Van Geem, W.H. Green, Combust. Flame (2013), http://dx.doi.org/10.1016/j.combustflame.2013.04.023.] and also shows impressive capabilities for predicting the new flame data presented here. The new set of data consists of isomer-resolved mole fraction profiles for more than 40 species in each of the four flames and provides a comprehensive benchmark for testing of any combustion chem. model for iso-butanol. Isomer-specificity is achieved by analyzing flames, which are burner-stabilized at equivalence ratios of .vphi. = 1.0-1.5 and at pressures between 15-30 Torr, with mol.-beam mass spectrometry and single-photon ionization by tunable vacuum-UV synchrotron radiation. Predictions of the C2H4O, C3H6O, and C4H8O enol-aldehyde-ketone isomers are improved compared to the earlier work by Hansen et al. [N. Hansen, M. R. Harper, W. H. Green, Phys. Chem. Chem. Phys. 13 (2011) 20262-20274] on similar n-butanol flames. A reaction path anal. identifies prominent fuel-consumption and oxidn. sequences. Almost all of the species mole fraction data reported here are predicted within the measurement uncertainties of a factor of two to three. Some significant differences with previous published models are highlighted.
- 102Slakman, B. L.; Simka, H.; Reddy, H.; West, R. H. Extending Reaction Mechanism Generator to Silicon Hydride Chemistry. Ind. Eng. Chem. Res. 2016, 55, 12507– 12515, DOI: 10.1021/acs.iecr.6b02402Google Scholar102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslOhsr%252FI&md5=51d944ea4978704bfbe0e0f68e7e0ca0Extending Reaction Mechanism Generator to Silicon Hydride ChemistrySlakman, Belinda L.; Simka, Harsono; Reddy, Harinath; West, Richard H.Industrial & Engineering Chemistry Research (2016), 55 (49), 12507-12515CODEN: IECRED; ISSN:0888-5885. (American Chemical Society)Understanding the gas-phase chem. of Si hydrides is the 1st step to building a realistic kinetic model for chem. vapor deposition (CVD). Functionality for thermodn. and kinetic data estn. of Si hydrides was added to the open-source software Reaction Mechanism Generator (RMG). Using the updated RMG, a detailed kinetic model was built for SiH4 thermal decompn. The generated model was used to perform reactor simulations at various process conditions for comparison to prior SiH4 decompn. expts. in a flow tube. Results show that the RMG-generated model can reasonably replicate exptl. results for SiH4 concn. profiles at different temps. and residence times. While the effect of changing initial SiH4 concn. is not captured, a 1st pass sensitivity anal. reveals that reasonable errors in reaction rates could contribute to the discrepancy.
- 103Seyedzadeh Khanshan, F.; West, R. H. Developing Detailed Kinetic Models of Syngas Production from Bio-Oil Gasification Using Reaction Mechanism Generator (RMG). Fuel 2016, 163, 25– 33, DOI: 10.1016/j.fuel.2015.09.031Google Scholar103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFersbjJ&md5=40a7d6183fcf086f287431148682cde2Developing detailed kinetic models of syngas production from bio-oil gasification using Reaction Mechanism Generator (RMG)Seyedzadeh Khanshan, Fariba; West, Richard H.Fuel (2016), 163 (), 25-33CODEN: FUELAC; ISSN:0016-2361. (Elsevier Ltd.)Detailed kinetic models for the conversion of bio-oil to syngas through gasification were developed automatically using the open source software package Reaction Mechanism Generator (RMG). The influences of process operating conditions and of RMG parameters on the performance of models were investigated. Both temp. and pressure alter the product yields, although including pressure-dependent (chem. activated and fall-off) kinetics have minimal impact on these predictions. The model size is important, although currently constrained by available RAM, motivating development of improved memory-management algorithms in RMG. To validate the RMG-built mechanisms, simulations performed with Cantera were compared with exptl. data from the literature. Agreements and disagreements between RMG-built models and literature show that the automated mechanism generation approach is promising, but reveal some families of reactions involving heteroat. cycles that require improved ests. for bio-mass derived fuels. Research in this area would be greatly helped by more quant. exptl. data, ideally showing intermediate species profiles. These findings motivate extra studies and guide further RMG development.
- 104Han, K.; Green, W. H.; West, R. H. On-the-Fly Pruning for Rate-Based Reaction Mechanism Generation. Comput. Chem. Eng. 2017, 100, 1– 8, DOI: 10.1016/j.compchemeng.2017.01.003Google Scholar104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXisVGgtLw%253D&md5=b48df5ab6c5e4d5f93447f5a562f8270On-the-fly pruning for rate-based reaction mechanism generationHan, Kehang; Green, William H.; West, Richard H.Computers & Chemical Engineering (2017), 100 (), 1-8CODEN: CCENDW; ISSN:0098-1354. (Elsevier B.V.)The no. of possible side reactions and byproduct species grows very rapidly with the size of a chem. mechanism. A memory-efficient algorithm for automated mechanism generation is presented for coping with this combinatorial complexity. The algorithm selects normalized flux as a metric to identify unimportant species during model generation and prunes them with their reactions, without any loss of accuracy. The new algorithm reduces memory requirements for building kinetic models with 200-300 species by about a factor of 4, or for fixed computer hardware makes it possible to create models including about twice as many species as was previously possible. The increased capability opens the possibility of discovering unexplored reaction networks and modeling more complicated reacting systems.
- 105Dana, A. G.; Buesser, B.; Merchant, S. S.; Green, W. H. Automated Reaction Mechanism Generation Including Nitrogen as a Heteroatom. Int. J. Chem. Kinet. 2018, 50, 243– 258, DOI: 10.1002/kin.21154Google Scholar105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVOqtbo%253D&md5=5ce0d70f40dea1ec2bea8cfac28998b0Automated Reaction Mechanism Generation Including Nitrogen as a HeteroatomDana, Alon Grinberg; Buesser, Beat; Merchant, Shamel S.; Green, William H.International Journal of Chemical Kinetics (2018), 50 (4), 243-258CODEN: IJCKBO; ISSN:0538-8066. (John Wiley & Sons, Inc.)The open source rate-based Reaction Mechanism Generator (RMG) software and its thermochem. and kinetics databases were extended to include nitrogen as a heteroatom. Specific changes to RMG and the mining of thermochem. and reaction kinetics data are discussed. This new version of RMG has been tested by generating a detailed pyrolysis and oxidn. model for ethylamine (EA, CH3CH2NH2) at ∼1400 K and ∼2 bar, and comparing it to recent shock tube studies. Validation of the reaction network with recent exptl. data showed that the generated model successfully reproduced the obsd. species as well as ignition delay measurements. During pyrolysis, EA initially decomps. via a C-C bond scission, and the CH2NH2 product subsequently produces the first H radicals in this system via β-scission. As the concn. of H increases, the major EA consuming reaction becomes H abstraction at the α-site by H radicals, leading to a chain reaction since its product generates more H radicals. During oxidn., the dominant N2-producing route is mediated by NO and N2O. The observables were found to be relatively sensitive to the C-C and C-N EA bond scission reactions as well as to the thermodn. values of EA; thermodn. data for EA were computed at the CBS-QB3 level and reported herein. This work demonstrates the ability of RMG to construct adequate kinetic models for nitrogenous species and discusses the pyrolysis and oxidn. mechanisms of EA.
- 106Grambow, C. A.; Jamal, A.; Li, Y.-P.; Green, W. H.; Zádor, J.; Suleimanov, Y. V. Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery Methods. J. Am. Chem. Soc. 2018, 140, 1035– 1048, DOI: 10.1021/jacs.7b11009Google Scholar106https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitVaksr%252FN&md5=cc0ce7340d7035db8729dd9cc71478d5Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery MethodsGrambow, Colin A.; Jamal, Adeel; Li, Yi-Pei; Green, William H.; Zador, Judit; Suleimanov, Yury V.Journal of the American Chemical Society (2018), 140 (3), 1035-1048CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Ketohydroperoxides are important in liq.-phase autoxidn. and in gas-phase partial oxidn. and pre-ignition chem., but because of their low concn., instability, and various anal. chem. limitations, it has been challenging to exptl. det. their reactivity, and only a few pathways are known. In the present work, 75 elementary-step unimol. reactions of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, were discovered by a combination of d. functional theory with several automated transition-state search algorithms: the Berny algorithm coupled with the freezing string method, single- and double-ended growing string methods, the heuristic KinBot algorithm, and the single-component artificial force induced reaction method (SC-AFIR). The present joint approach significantly outperforms previous manual and automated transition-state searches - 68 of the reactions of γ-ketohydroperoxide discovered here were previously unknown and completely unexpected. All of the methods found the lowest-energy transition state, which corresponds to the first step of the Korcek mechanism, but each algorithm except for SC-AFIR detected several reactions not found by any of the other methods. We show that the low-barrier chem. reactions involve promising new chem. that may be relevant in atm. and combustion systems. Our study highlights the complexity of chem. space exploration and the advantage of combined application of several approaches. Overall, the present work demonstrates both the power and the weaknesses of existing fully automated approaches for reaction discovery which suggest possible directions for further method development and assessment in order to enable reliable discovery of all important reactions of any specified reactant(s).
- 107Suleimanov, Y. V.; Green, W. H. Automated Discovery of Elementary Chemical Reaction Steps Using Freezing String and Berny Optimization Methods. J. Chem. Theory Comput. 2015, 11, 4248, DOI: 10.1021/acs.jctc.5b00407Google Scholar107https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1Srsb7I&md5=d430c76d756be29d6c52befc113e6400Automated Discovery of Elementary Chemical Reaction Steps Using Freezing String and Berny Optimization MethodsSuleimanov, Yury V.; Green, William H.Journal of Chemical Theory and Computation (2015), 11 (9), 4248-4259CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We present a simple protocol which allows fully automated discovery of elementary chem. reaction steps using in cooperation double- and single-ended transition-state optimization algorithms - the freezing string and Berny optimization methods, resp. To demonstrate the utility of the proposed approach, the reactivity of several single-mol. systems of combustion and atm. chem. importance is investigated. The proposed algorithm allowed us to detect without any human intervention not only "known" reaction pathways, manually detected in the previous studies, but also new, previously "unknown", reaction pathways which involve significant atom rearrangements. We believe that applying such a systematic approach to elementary reaction path finding will greatly accelerate the discovery of new chem. and will lead to more accurate computer simulations of various chem. processes.
- 108Schlegel, H. B. Optimization of Equilibrium Geometries and Transition Structures. J. Comput. Chem. 1982, 3, 214– 218, DOI: 10.1002/jcc.540030212Google Scholar108https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL38XktFajtrY%253D&md5=81448fcccb0620eff4b6754171e84f70Optimization of equilibrium geometries and transition structuresSchlegel, H. BernhardJournal of Computational Chemistry (1982), 3 (2), 214-18CODEN: JCCHDD; ISSN:0192-8651.A modified conjugate gradient algorithm for geometry optimization is outlined for use with ab initio MO methods. Since the computation time for anal. energy gradients is approx. the same as for the energy, the optimization algorithm evaluates and utilizes the gradients each time the energy is computed. The second deriv. matrix, rather than its inverse, is updated employing the gradients. At each step, a one-dimensional minimization using a quartic polynomial is carried out, followed by an n-dimensional search using the second deriv. matrix. By suitably controlling the no. of neg. eigenvalues of the second deriv. matrix, the algorithm can also be used to locate transition structures. Representative timeing data for optimizations of equil. geometries and transition structures are reported for ab initio SCF-MO calcns.
- 109Schlegel, H. B. Estimating the Hessian for Gradient-Type Geometry Optimizations. Theoret. Chim. Acta 1984, 66, 333– 340, DOI: 10.1007/BF00554788
- 110Peng, C.; Ayala, P. Y.; Schlegel, H. B.; Frisch, M. J. Using Redundant Internal Coordinates to Optimize Equilibrium Geometries and Transition States. J. Comput. Chem. 1996, 17, 49– 56, DOI: 10.1002/(SICI)1096-987X(19960115)17:1<49::AID-JCC5>3.0.CO;2-0Google Scholar110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XpvFSi&md5=330450a8e3f31abc94db9435cfe23935Using redundant internal coordinates to optimize equilibrium geometries and transition statesPeng, Chunyang; Ayala, Philippe; Schlegel, H. Bernhard; Frisch, Michael J.Journal of Computational Chemistry (1996), 17 (1), 49-56CODEN: JCCHDD; ISSN:0192-8651. (Wiley)A redundant internal coordinate system for optimizing mol. geometries is constructed from all bonds, all valence angles between bonded atoms, and all dihedral angles between bonded atoms. Redundancies are removed by using the generalized inverse of the G matrix; constraints can be added by using an appropriate projects. For minimizations, redundant internal coordinates provide substantial improvements in optimization efficiency over Cartesian and nonredundant internal coordinates, esp. for flexible and polycyclic systems. Transition structure searches are also improved when redundant coordinates are used and when the initial steps are guided by the quadratic synchronous transit approach.
- 111Bhoorasingh, P. L.; West, R. H. Transition State Geometry Prediction Using Molecular Group Contributions. Phys. Chem. Chem. Phys. 2015, 17, 32173– 32182, DOI: 10.1039/C5CP04706DGoogle Scholar111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFKhtb3P&md5=16e7f411e54e0417dfd07bbf66ac66b2Transition state geometry prediction using molecular group contributionsBhoorasingh, Pierre L.; West, Richard H.Physical Chemistry Chemical Physics (2015), 17 (48), 32173-32182CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Detailed kinetic models to aid the understanding of complex chem. systems require many thousands of reaction rate coeffs., most of which are estd., some quite approx. and with unknown uncertainties. This motivates the development of high-throughput methods to det. rate coeffs. via transition state theory calcns., which requires the automatic prediction of transition state (TS) geometries. We demonstrate a novel approach to predict TS geometries using a group-additive method. Distances between reactive atoms at the TS are estd. using mol. group values, with the 3D geometry of the TS being constructed by distance geometry. The est. is then optimized using electronic structure theory and validated using intrinsic reaction coordinate calcns., completing the fully automatic algorithm to locate TS geometries. The methods were tested using a diisopropyl ketone combustion model contg. 1393 hydrogen abstraction reactions, of which transition states were found for 907 over two iterations of the algorithm. With sufficient training data, mol. group contributions were shown to successfully predict the reaction center distances of transition states with root-mean-squared errors of only 0.04 Å.
- 112Rappoport, D.; Galvin, C. J.; Zubarev, D. Y.; Aspuru-Guzik, A. Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry. J. Chem. Theory Comput. 2014, 10, 897– 907, DOI: 10.1021/ct401004rGoogle Scholar112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVOqurY%253D&md5=64f81a54964e1e07a08421b61e45f495Complex Chemical Reaction Networks from Heuristics-Aided Quantum ChemistryRappoport, Dmitrij; Galvin, Cooper J.; Zubarev, Dmitry Yu.; Aspuru-Guzik, AlanJournal of Chemical Theory and Computation (2014), 10 (3), 897-907CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)While structures and reactivities of many small mols. can be computed efficiently and accurately using quantum chem. methods, heuristic approaches remain essential for modeling complex structures and large-scale chem. systems. Here, we present a heuristics-aided quantum chem. methodol. applicable to complex chem. reaction networks such as those arising in cell metab. and prebiotic chem. Chem. heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chem. structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chem. methodol. to the formose reaction reproduces the exptl. obsd. reaction products, major reaction pathways, and autocatalytic cycles.
- 113Zubarev, D. Y.; Rappoport, D.; Aspuru-Guzik, A. Uncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid Cycle. Sci. Rep. 2015, 5, 8009, DOI: 10.1038/srep08009Google Scholar113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXotlagsrs%253D&md5=76b8b2e61796a6a68b76dd84a9e3b45dUncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid CycleZubarev, Dmitry Yu; Rappoport, Dmitrij; Aspuru-Guzik, AlanScientific Reports (2015), 5 (), 8009/1-8009/7CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)We consider the hypothesis of the primordial nature of the non-enzymic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chem. transformations. Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.
- 114Rappoport, D.; Aspuru-Guzik, A. Predicting Feasible Organic Reaction Pathways Using Heuristically Aided Quantum Chemistry. ChemRxiv Preprint 2018, DOI: 10.26434/chemrxiv.6649565.v1
- 115Butlerow, A. Bildung einer zuckerartigen Substanz durch Synthese. Justus Liebigs Ann. Chem. 1861, 120, 295– 298, DOI: 10.1002/jlac.18611200308
- 116Levy, D. E. Arrow-Pushing in Organic Chemistry: An Easy Approach to Understanding Reaction Mechanisms, 2nd ed.; Wiley, 2017.Google ScholarThere is no corresponding record for this reference.
- 117Kim, Y.; Woo Kim, J.; Kim, Z.; Youn Kim, W. Efficient Prediction of Reaction Paths through Molecular Graph and Reaction Network Analysis. Chem. Sci. 2018, 9, 825– 835, DOI: 10.1039/C7SC03628KGoogle Scholar117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFGnsbjI&md5=71d81e16d0ac1ee7164da8f664e8dcbbEfficient prediction of reaction paths through molecular graph and reaction network analysisKim, Yeonjoon; Kim, Jin Woo; Kim, Zeehyo; Kim, Woo YounChemical Science (2018), 9 (4), 825-835CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)Despite remarkable advances in computational chem., prediction of reaction mechanisms is still challenging, because investigating all possible reaction pathways is computationally prohibitive due to the high complexity of chem. space. A feasible strategy for efficient prediction is to utilize chem. heuristics. Here, we propose a novel approach to rapidly search reaction paths in a fully automated fashion by combining chem. theory and heuristics. A key idea of our method is to ext. a minimal reaction network composed of only favorable reaction pathways from the complex chem. space through mol. graph and reaction network anal. This can be done very efficiently by exploring the routes connecting reactants and products with min. dissocn. and formation of bonds. Finally, the resulting minimal network is subjected to quantum chem. calcns. to det. kinetically the most favorable reaction path at the predictable accuracy. As example studies, our method was able to successfully find the accepted mechanisms of Claisen ester condensation and cobalt-catalyzed hydroformylation reactions.
- 118Zimmerman, P. M. Automated Discovery of Chemically Reasonable Elementary Reaction Steps. J. Comput. Chem. 2013, 34, 1385– 1392, DOI: 10.1002/jcc.23271Google Scholar118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXktFWhtb4%253D&md5=443c5c1be4f67d956c120a64a77ee82dAutomated discovery of chemically reasonable elementary reaction stepsZimmerman, Paul M.Journal of Computational Chemistry (2013), 34 (16), 1385-1392CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Due to the significant human effort and chem. intuition required to locate chem. reaction pathways with quantum chem. modeling, only a small subspace of possible reactions is usually studied for any given system. Herein, a systematic approach is proposed for locating reaction paths that bypasses the required human effort and expands the reactive search space, all while maintaining low computational cost. To achieve this, a range of intermediates are generated that represent potential single elementary steps away from a starting structure. These structures are then screened to identify those that are thermodynamically accessible, and then feasible reaction paths to the remaining structures are located. This strategy for elementary reaction path finding is independent of atomistic model whenever bond breaking and forming are properly described. The approach is demonstrated to work well for upper main group elements, but this limitation can easily be surpassed. Further extension will allow discovery of multistep reaction mechanisms in a single computation. The method is highly parallel, allowing for effective use of modern large-scale computational clusters. © 2013 Wiley Periodicals, Inc.
- 119Zimmerman, P. M. Navigating Molecular Space for Reaction Mechanisms: An Efficient, Automated Procedure. Mol. Simul. 2015, 41, 43– 54, DOI: 10.1080/08927022.2014.894999Google Scholar119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltFait7k%253D&md5=4e996b3b2f43c78843468df3e622b79aNavigating molecular space for reaction mechanisms: an efficient, automated procedureZimmerman, Paul M.Molecular Simulation (2015), 41 (1-3), 43-54CODEN: MOSIEA; ISSN:0892-7022. (Taylor & Francis Ltd.)A review; mechanism is a core chem. concept that has vital implications for reaction rate, efficiency and selectivity. The discovery of mechanism is not easy due to the great diversity of possible chem. rearrangements in even relatively simple systems. For this reason, mechanisms involving bond breaking and forming are usually proposed via chem. intuition - which limits the scope of considered possibilities - and these hypotheses are then tested using simulation or expt. This article discusses an automated simulation strategy for investigating multiple elementary step reaction mechanisms in chem. systems. The method starts from a single input structure and seeks out nearby intermediates, optimizes the proposed structures and then dets. the kinetic viability of each elementary step. The kinetically accessible intermediates are catalogued and new searches are performed on each unique structure. This process is repeated for an arbitrary no. of steps without human intervention, and massively parallel computation enables fast searches in chem. space. Importantly, this strategy can be empirically shown to lead to a finite no. of accessible structures, not a combinatorial explosion of intermediates. Therefore, the method should be able to predict multi-step reaction pathways in many interesting chem. systems. Demonstrations on org. reactions and a hydrogen storage material, ammonia borane, show that the herein proposed strategy can uncover complex reactivity without relying on existing chem. intuition.
- 120Zimmerman, P. M. Growing String Method with Interpolation and Optimization in Internal Coordinates: Method and Examples. J. Chem. Phys. 2013, 138, 184102, DOI: 10.1063/1.4804162Google Scholar120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsV2isLg%253D&md5=e315e6f2a3e4e1bf65e743d1ee3863b5Growing string method with interpolation and optimization in internal coordinates: Method and examplesZimmerman, Paul M.Journal of Chemical Physics (2013), 138 (18), 184102/1-184102/10CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The growing string method (GSM) has proven esp. useful for locating chem. reaction paths at low computational cost. While many string methods use Cartesian coordinates, these methods can be substantially improved by changes in the coordinate system used for interpolation and optimization steps. The quality of the interpolation scheme is esp. important because it dets. how close the initial path is to the optimized reaction path, and this strongly affects the rate of convergence. In this article, a detailed description of the generation of internal coordinates (ICs) suitable for use in GSM as reactive tangents and in string optimization is given. Convergence of reaction paths is smooth because the IC tangent and orthogonal directions are better representations of chem. bonding compared to Cartesian coordinates. This is not only important quant. for reducing computational cost but also allows reaction paths to be described with smoothly varying chem. relevant coordinates. Benchmark computations with challenging reactions are compared to previous versions of GSM and show significant speedups. Finally, a climbing image scheme is included to improve the quality of the transition state approxn., ensuring high reliability of the method. (c) 2013 American Institute of Physics.
- 121Zimmerman, P. M. Single-Ended Transition State Finding with the Growing String Method. J. Comput. Chem. 2015, 36, 601– 611, DOI: 10.1002/jcc.23833Google Scholar121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXltVKlsQ%253D%253D&md5=4b3087ccfd79ea3fba13820a2be013e3Single-ended transition state finding with the growing string methodZimmerman, Paul M.Journal of Computational Chemistry (2015), 36 (9), 601-611CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Reaction path finding and transition state (TS) searching are important tasks in computational chem. Methods that seek to optimize an evenly distributed set of structures to represent a chem. reaction path are known as double-ended string methods. Such methods can be highly reliable because the endpoints of the string are fixed, which effectively lowers the dimensionality of the reaction path search. String methods, however, require that the reactant and product structures are known beforehand, which limits their ability for systematic exploration of reactive steps. In this article, a single-ended growing string method (GSM) is introduced which allows for reaction path searches starting from a single structure. The method works by sequentially adding nodes along coordinates that drive bonds, angles, and/or torsions to a desired reactive outcome. After the string is grown and an approx. reaction path through the TS is found, string optimization commences and the exact TS is located along with the reaction path. Fast convergence of the string is achieved through use of internal coordinates and eigenvector optimization schemes combined with Hessian ests. Comparison to the double-ended GSM shows that single-ended method can be even more computationally efficient than the already rapid double-ended method. Examples, including transition metal reactivity and a systematic, automated search for unknown reactivity, demonstrate the efficacy of the new method. This automated reaction search is able to find 165 reaction paths from 333 searches for the reaction of NH3BH3 and (LiH)4, all without guidance from user intuition. © 2015 Wiley Periodicals, Inc.
- 122Jafari, M.; Zimmerman, P. M. Reliable and Efficient Reaction Path and Transition State Finding for Surface Reactions with the Growing String Method. J. Comput. Chem. 2017, 38, 645– 658, DOI: 10.1002/jcc.24720Google Scholar122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslSju74%253D&md5=a8441a251705eefd13a4c844ad88da74Reliable and efficient reaction path and transition state finding for surface reactions with the growing string methodJafari, Mina; Zimmerman, Paul M.Journal of Computational Chemistry (2017), 38 (10), 645-658CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)The computational challenge of fast and reliable transition state and reaction path optimization requires new methodol. strategies to maintain low cost, high accuracy, and systematic searching capabilities. The growing string method using internal coordinates has proven to be highly effective for the study of mol., gas phase reactions, but difficulties in choosing a suitable coordinate system for periodic systems has prevented its use for surface chem. New developments are therefore needed, and presented herein, to handle surface reactions which include atoms with large coordination nos. that cannot be treated using std. internal coordinates. The double-ended and single-ended growing string methods are implemented using a hybrid coordinate system, then benchmarked for a test set of 43 elementary reactions occurring on surfaces. These results show that the growing string method is at least 45% faster than the widely used climbing image-nudged elastic band method, which also fails to converge in several of the test cases. Addnl., the surface growing string method has a unique single-ended search method which can move outward from an initial structure to find the intermediates, transition states, and reaction paths simultaneously. This powerful explorative feature of single ended-growing string method is demonstrated to uncover, for the first time, the mechanism for at. layer deposition of TiN on Cu(111) surface. This reaction is found to proceed through multiple hydrogen-transfer and ligand-exchange events, while formation of H-bonds stabilizes intermediates of the reaction. Purging gaseous products out of the reaction environment is the driving force for these reactions. © 2017 Wiley Periodicals, Inc.
- 123Nett, A. J.; Zhao, W.; Zimmerman, P. M.; Montgomery, J. Highly Active Nickel Catalysts for C–H Functionalization Identified through Analysis of Off-Cycle Intermediates. J. Am. Chem. Soc. 2015, 137, 7636– 7639, DOI: 10.1021/jacs.5b04548Google Scholar123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVansLzJ&md5=a505b5a761d3a525a26dbb20f9b815e9Highly Active Nickel Catalysts for C-H Functionalization Identified through Analysis of Off-Cycle IntermediatesNett, Alex J.; Zhao, Wanxiang; Zimmerman, Paul M.; Montgomery, JohnJournal of the American Chemical Society (2015), 137 (24), 7636-7639CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)An inhibitory role of 1,5-cyclooctadiene (COD) in nickel-catalyzed C-H functionalization processes was identified and studied. The bound COD participates in C-H activation by capturing the hydride, leading to a stable off-cycle π-allyl complex that greatly diminished overall catalytic efficiency. Computational studies elucidated the origin of the effect and enabled identification of a 1,5-hexadiene-derived pre-catalyst that avoids the off-cycle intermediate and provides catalytic efficiencies that are superior to those of catalysts derived from Ni(COD)2.
- 124Li, M. W.; Pendleton, I. M.; Nett, A. J.; Zimmerman, P. M. Mechanism for Forming B,C,N,O Rings from NH3BH3and vCO2ia Reaction Discovery Computations. J. Phys. Chem. A 2016, 120, 1135– 1144, DOI: 10.1021/acs.jpca.5b11156
- 125Pendleton, I. M.; Pérez-Temprano, M. H.; Sanford, M. S.; Zimmerman, P. M. Experimental and Computational Assessment of Reactivity and Mechanism in C(sp3)–N Bond-Forming Reductive Elimination from Palladium(IV). J. Am. Chem. Soc. 2016, 138, 6049– 6060, DOI: 10.1021/jacs.6b02714Google Scholar125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmtF2murk%253D&md5=f739ebd816c70d6b9930b82153ca7aa7Experimental and Computational Assessment of Reactivity and Mechanism in C(sp3)-N Bond-Forming Reductive Elimination from Palladium(IV)Pendleton, Ian M.; Perez-Temprano, Monica H.; Sanford, Melanie S.; Zimmerman, Paul M.Journal of the American Chemical Society (2016), 138 (18), 6049-6060CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)This report describes a combined exptl. and computational investigation of the mechanism of C(sp3)-N bond-forming reductive elimination from sulfonamide-ligated PdIV complexes. After an initial exptl. assessment of reactivity, we used ZStruct, a computational combinatorial reaction finding method, to analyze a large no. of multistep mechanisms for this process. This study reveals two facile isomerization pathways connecting the exptl. obsd. PdIV isomers, along with two competing SN2 pathways for C(sp3)-N coupling. One of these pathways involves an unanticipated oxygen-nitrogen exchange of the sulfonamide ligand prior to an inner-sphere SN2-type reductive elimination. The calcd. ΔG⧺ values for isomerization and reductive elimination with a series of sulfonamide derivs. are in good agreement with exptl. data. Furthermore, the simulations predict relative reaction rates with different sulfonamides, which is successful only after considering competition between the proposed operating mechanisms. Overall, this work shows that the combination of exptl. studies and new computational tools can provide fundamental mechanistic insights into complex organometallic reaction pathways.
- 126Zhao, Y.; Nett, A. J.; McNeil, A. J.; Zimmerman, P. M. Computational Mechanism for Initiation and Growth of Poly(3-Hexylthiophene) Using Palladium N-Heterocyclic Carbene Precatalysts. Macromolecules 2016, 49, 7632– 7641, DOI: 10.1021/acs.macromol.6b01648
- 127Dewyer, A. L.; Zimmerman, P. M. Finding Reaction Mechanisms, Intuitive or Otherwise. Org. Biomol. Chem. 2017, 15, 501– 504, DOI: 10.1039/C6OB02183BGoogle Scholar127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVyjtbjJ&md5=1f70486f3755a036f7a878bbf98bc52bFinding reaction mechanisms, intuitive or otherwiseDewyer, Amanda L.; Zimmerman, Paul M.Organic & Biomolecular Chemistry (2017), 15 (3), 501-504CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)Chem. reaction mechanisms have been frequently studied using computational simulations, but these tools have been primarily effective at examg. reaction paths within the scope of chem. intuition. To det. reaction mechanisms that were not already preconceived by chemists, nonstandard simulation tools are required. This perspective introduces new methods developed by the Zimmerman group that are designed to uncover sequences of elementary steps, from first principles and without substantial human guidance. Results from the areas of organo catalysis and transition metal catalysis indicate that new frontiers of knowledge will be gained through continued development and application of reaction discovery simulation techniques.
- 128Ludwig, J. R.; Zimmerman, P. M.; Gianino, J. B.; Schindler, C. S. Iron(III)-Catalysed Carbonyl–Olefin Metathesis. Nature 2016, 533, 374– 379, DOI: 10.1038/nature17432Google Scholar128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmvVGntrY%253D&md5=4763c79022c8121eef0dc857214954dbIron(III)-catalysed carbonyl-olefin metathesisLudwig, Jacob R.; Zimmerman, Paul M.; Gianino, Joseph B.; Schindler, Corinna S.Nature (London, United Kingdom) (2016), 533 (7603), 374-379CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)The olefin metathesis reaction of two unsatd. substrates is one of the most powerful carbon-carbon-bond-forming reactions in org. chem. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of mols. relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.
- 129Smith, M. L.; Leone, A. K.; Zimmerman, P. M.; McNeil, A. J. Impact of Preferential π-Binding in Catalyst-Transfer Polycondensation of Thiazole Derivatives. ACS Macro Lett. 2016, 5, 1411– 1415, DOI: 10.1021/acsmacrolett.6b00886Google Scholar129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVejsLbP&md5=ecff32183eb4d751c490869b57211ab3Impact of Preferential π-Binding in Catalyst-Transfer Polycondensation of Thiazole DerivativesSmith, Mitchell L.; Leone, Amanda K.; Zimmerman, Paul M.; McNeil, Anne J.ACS Macro Letters (2016), 5 (12), 1411-1415CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)Polymg. electron-deficient arenes in a controlled, chain-growth fashion remains a significant challenge despite a decade of research on catalyst-transfer polycondensation. The prevailing hypothesis is that the chain-growth mechanism stalls at a strongly assocd. metal-polymer π-complex, preventing catalyst turnover. To evaluate this hypothesis, we performed mechanistic studies using thiazole derivs. and identified approaches to improve their chain-growth polymn. These studies revealed a surprisingly high barrier for chain-walking toward the reactive C-X bond. In addn., a competitive pathway involving chain-transfer to monomer was identified. This pathway is facilitated by ancillary ligand dissocn. and N-coordination to the incoming monomer. We found that this chain-transfer pathway can be attenuated by using a rigid ancillary ligand, leading to an improved polymn. Combined, these studies provide mechanistic insight into the challenges assocd. with electron-deficient monomers and ways to improve their living, chain-growth polymn. Our mechanistic studies also revealed an unexpected radical anion-mediated oligomerization in the absence of catalyst, and a surprising oxidative addn. into the thiazole C-S bond in a model system.
- 130Ludwig, J. R.; Phan, S.; McAtee, C. C.; Zimmerman, P. M.; Devery, J. J.; Schindler, C. S. Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis Reaction. J. Am. Chem. Soc. 2017, 139, 10832– 10842, DOI: 10.1021/jacs.7b05641Google Scholar130https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1egt7jM&md5=4a6fef8b15abcdf907ae50c6cfda4874Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis ReactionLudwig, Jacob R.; Phan, Susan; McAtee, Christopher C.; Zimmerman, Paul M.; Devery, James J., III; Schindler, Corinna S.Journal of the American Chemical Society (2017), 139 (31), 10832-10842CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Iron(III)-catalyzed carbonyl-olefin ring-closing metathesis represents a new approach toward the assembly of mols. traditionally generated by olefin-olefin metathesis or olefination. Herein, we report detailed synthetic, spectroscopic, kinetic, and computational studies to det. the mechanistic features imparted by iron(III), substrate, and temp. to the catalytic cycle. These data are consistent with an iron(III)-mediated asynchronous, concerted [2+2]-cycloaddn. to form an intermediate oxetane as the turnover-limiting step. Fragmentation of the oxetane via Lewis acid-activation results in the formation of five- and six-membered unsatd. carbocycles.
- 131Dewyer, A. L.; Zimmerman, P. M. Simulated Mechanism for Palladium-Catalyzed, Directed γ-Arylation of Piperidine. ACS Catal. 2017, 7, 5466– 5477, DOI: 10.1021/acscatal.7b01390Google Scholar131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1SjtrrL&md5=6411ffbbfdd8b838027c426c5c1ca207Simulated Mechanism for Palladium-Catalyzed, Directed γ-Arylation of PiperidineDewyer, Amanda L.; Zimmerman, Paul M.ACS Catalysis (2017), 7 (8), 5466-5477CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Quantum chem. reaction path finding methods are herein used to investigate the mechanism of Pd-catalyzed distal functionalization of piperidine, as reported by Sanford. These methods allowed navigation of a complex reaction landscape with multiple reactants interacting at all key steps of the proposed catalytic cycle. A multistep cycle is shown to conceptually begin with substrate ligation and Pd(II)-catalyzed C-H activation, which occurs through concerted metalation-deprotonation. In subsequent steps, the kinetic and thermodn. profiles for oxidative addn., reductive elimination, and catalyst regeneration show why excess Cs salts and ArI were required in the expt. Specifically, excess ArI is necessary to thermodynamically overcome the high energy of the C-H activated intermediate and allow oxidative addn. to be favorable, and excess Cs salt is needed to sequester reaction byproducts during oxidative addn. and catalyst regeneration. The overall catalytic profile is consistent with rate-limiting C-H activation, explains the probable functions of all major exptl. conditions, and gives atomistic detail to guide expt. to improve this challenging transformation even further.
- 132Habershon, S. Sampling Reactive Pathways with Random Walks in Chemical Space: Applications to Molecular Dissociation and Catalysis. J. Chem. Phys. 2015, 143, 094106, DOI: 10.1063/1.4929992Google Scholar132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVCms73P&md5=10d9945d033f6fcbdf91a9a4859d4243Sampling reactive pathways with random walks in chemical space: Applications to molecular dissociation and catalysisHabershon, ScottJournal of Chemical Physics (2015), 143 (9), 094106/1-094106/14CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Automatically generating chem. reaction pathways is a significant computational challenge, particularly in the case where a given chem. system can exhibit multiple reactants and products, as well as multiple pathways connecting these. Here, we outline a computational approach to allow automated sampling of chem. reaction pathways, including sampling of different chem. species at the reaction end-points. The key features of this scheme are (i) introduction of a Hamiltonian which describes a reaction "string" connecting reactant and products, (ii) definition of reactant and product species as chem. connectivity graphs, and (iii) development of a scheme for updating the chem. graphs assocd. with the reaction end-points. By performing mol. dynamics sampling of the Hamiltonian describing the complete reaction pathway, we are able to sample multiple different paths in configuration space between given chem. products; by periodically modifying the connectivity graphs describing the chem. identities of the end-points we are also able to sample the allowed chem. space of the system. Overall, this scheme therefore provides a route to automated generation of a "roadmap" describing chem. reactivity. This approach is first applied to model dissocn. pathways in formaldehyde, H2CO, as described by a parameterised potential energy surface (PES). A second application to the HCo(CO)3 catalyzed hydroformylation of ethene (oxo process), using d. functional tight-binding to model the PES, demonstrates that our graph-based approach is capable of sampling the intermediate paths in the commonly accepted catalytic mechanism, as well as several secondary reactions. Further algorithmic improvements are suggested which will pave the way for treating complex multi-step reaction processes in a more efficient manner. (c) 2015 American Institute of Physics.
- 133Habershon, S. Automated Prediction of Catalytic Mechanism and Rate Law Using Graph-Based Reaction Path Sampling. J. Chem. Theory Comput. 2016, 12, 1786– 1798, DOI: 10.1021/acs.jctc.6b00005Google Scholar133https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xjs1Sqtbk%253D&md5=f227bc5d2e1be8e62e71c72bf772bb71Automated Prediction of Catalytic Mechanism and Rate Law Using Graph-Based Reaction Path SamplingHabershon, ScottJournal of Chemical Theory and Computation (2016), 12 (4), 1786-1798CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)In a recent article [ J. Chem. Phys. 2015, 143, 094106], we introduced a novel graph-based sampling scheme which can be used to generate chem. reaction paths in many-atom systems in an efficient and highly automated manner. The main goal of this work is to demonstrate how this approach, when combined with direct kinetic modeling, can be used to det. the mechanism and phenomenol. rate law of a complex catalytic cycle, namely cobalt-catalyzed hydroformylation of ethene. Our graph-based sampling scheme generates 31 unique chem. products and 32 unique chem. reaction pathways; these sampled structures and reaction paths enable automated construction of a kinetic network model of the catalytic system when combined with d. functional theory (DFT) calcns. of free energies and resultant transition-state theory rate consts. Direct simulations of this kinetic network across a range of initial reactant concns. enables detn. of both the reaction mechanism and the assocd. rate law in an automated fashion, without the need for either presupposing a mechanism or making steady-state approxns. in kinetic anal. Most importantly, we find that the reaction mechanism which emerges from these simulations is exactly that originally proposed by Heck and Breslow; furthermore, the simulated rate law is also consistent with previous exptl. and computational studies, exhibiting a complex dependence on carbon monoxide pressure. While the inherent errors of using DFT simulations to model chem. reactivity limit the quant. accuracy of our calcd. rates, this work confirms that our automated simulation strategy enables direct anal. of catalytic mechanisms from first principles.
- 134Wheeler, S. E.; Seguin, T. J.; Guan, Y.; Doney, A. C. Noncovalent Interactions in Organocatalysis and the Prospect of Computational Catalyst Design. Acc. Chem. Res. 2016, 49, 1061– 1069, DOI: 10.1021/acs.accounts.6b00096Google Scholar134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmsFCrsLw%253D&md5=4cffcbf91f93ae4ecaf20537c364fcebNoncovalent Interactions in Organocatalysis and the Prospect of Computational Catalyst DesignWheeler, Steven E.; Seguin, Trevor J.; Guan, Yanfei; Doney, Analise C.Accounts of Chemical Research (2016), 49 (5), 1061-1069CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Noncovalent interactions are ubiquitous in org. systems, and can play decisive roles in the outcome of asym. organocatalytic reactions. Their prevalence, combined with the often subtle line sepg. favorable dispersion interactions from unfavorable steric interactions, often complicates the identification of the particular noncovalent interactions responsible for stereoselectivity. Ultimately, the stereoselectivity of most organocatalytic reactions hinges on the balance of both favorable and unfavorable noncovalent interactions in the stereocontrolling transition state (TS). In this Account, we provide an overview of our attempts to understand the role of noncovalent interactions in organocatalyzed reactions and to develop new computational tools for organocatalyst design. Following a brief discussion of noncovalent interactions involving arom. rings and the assocd. challenges capturing these effects computationally, we summarize two examples of chiral phosphoric acid catalyzed reactions in which noncovalent interactions play pivotal, although somewhat unexpected, roles. In the first, List's catalytic asym. Fischer indole reaction, we show that both π-stacking and CH/π interactions of the substrate with the 3,3'-aryl groups of the catalyst impact the stability of the stereocontrolling TS. However, these noncovalent interactions oppose each other, with π-stacking interactions stabilizing the TS leading to one enantiomer and CH/π interactions preferentially stabilizing the competing TS. Ultimately, the CH/π interactions dominate and, when combined with hydrogen bonding interactions, lead to preferential formation of the obsd. product. In the second example, a series of phosphoric acid catalyzed asym. ring openings of meso-epoxides, we show that noncovalent interactions of the substrates with the 3,3'-aryl groups of the catalyst play only an indirect role in stereoselectivity. Instead, the stereoselectivity of these reactions are driven by the electrostatic stabilization of a fleeting partial pos. charge in the SN2-like transition state by the chiral electrostatic environment of the phosphoric acid catalyst. Next, we describe our studies of bipyridine N-oxide and N,N'-dioxide catalyzed alkylation reactions. Based on several examples, we demonstrate that there are many potential arrangements of ligands around a hexacoordinate silicon in the stereocontrolling TS, and one must consider all of these in order to identify the lowest-lying TS structures. We also present a model in which electrostatic interactions between a formyl CH group and a chlorine in these TSs underlie the enantioselectivity of these reactions. Finally, we discuss our efforts to develop computational tools for the screening of potential organocatalyst designs, starting in the context of bipyridine N,N'-dioxide catalyzed alkylation reactions. Our new computational tool kit (AARON) has been used to design highly effective catalysts for the asym. propargylation of benzaldehyde, and is currently being used to screen catalysts for other reactions. We conclude with our views on the potential roles of computational chem. in the future of organocatalyst design.
- 135Doney, A. C.; Rooks, B. J.; Lu, T.; Wheeler, S. E. Design of Organocatalysts for Asymmetric Propargylations through Computational Screening. ACS Catal. 2016, 6, 7948– 7955, DOI: 10.1021/acscatal.6b02366Google Scholar135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1yks7jO&md5=207d00d90bba03b6dfeed14f3762364aDesign of Organocatalysts for Asymmetric Propargylations through Computational ScreeningDoney, Analise C.; Rooks, Benjamin J.; Lu, Tongxiang; Wheeler, Steven E.ACS Catalysis (2016), 6 (11), 7948-7955CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)The development of asym. catalysts is typically driven by the exptl. screening of potential catalyst designs. Herein, the authors demonstrate the design of asym. propargylation catalysts through computational screening. This was done using computational toolkit AARON (automated alkylation reaction optimizer for N-oxides), which automates the prediction of enantioselectivities for bidentate Lewis base catalyzed alkylation reactions. A systematic screening of 59 potential catalysts built on 6 bipyridine N,N'-dioxide-derived scaffolds results in predicted ee values for the propargylation of benzaldehyde ranging from 45% (S) to 99% (R), with 12 ee values exceeding 95%. These data provide a broad set of exptl. testable predictions. Also, the assocd. data revealed key details regarding the role of stabilizing electrostatic interactions in asym. propargylations, which were harnessed in the design of a propargylation catalyst for which the predicted ee exceeds 99%.
- 136Guan, Y.; Wheeler, S. E. Automated Quantum Mechanical Predictions of Enantioselectivity in a Rhodium-Catalyzed Asymmetric Hydrogenation. Angew. Chem. 2017, 129, 9229– 9233, DOI: 10.1002/ange.201704663
- 137Guan, Y.; Ingman, V. M.; Rooks, B. J.; Wheeler, S. E. AARON: An Automated Reaction Optimizer for New Catalysts. J. Chem. Theory Comput. 2018, 14, 5249, DOI: 10.1021/acs.jctc.8b00578Google Scholar137https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVOlsbbO&md5=f8e15c28a5e202415fbb232e93310a79AARON: An Automated Reaction Optimizer for New CatalystsGuan, Yanfei; Ingman, Victoria M.; Rooks, Benjamin J.; Wheeler, Steven E.Journal of Chemical Theory and Computation (2018), 14 (10), 5249-5261CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We describe an open-source computational toolkit (AARON: An Automated Reaction Optimizer for New catalysts) that automates the quantum mech. geometry optimization and characterization of the transition state and intermediate structures required to predict the activities and selectivities of asym. catalytic reactions. Modern computational quantum chem. has emerged as a powerful tool for explaining the selectivity and activity of asym. catalysts. However, reliably predicting the stereochem. outcome of realistic reactions often requires the geometry optimization of hundreds of transition state and intermediate structures, which is a tedious process. AARON automates these optimizations through an interface with a popular electronic structure package, accelerating quantum chem. workflows to enable the computational screening of potential catalysts. AARON is built using a collection of object-oriented Perl modules (AaronTools) that provide functionality to build and modify mol. and supramol. structures. The main functionalities of AaronTools are also available as stand-alone command-line scripts. The core features of AaronTools and AARON are explained, and representative applications of AARON to both organocatalyzed and transition-metal-catalyzed reactions are presented.
- 138Geerlings, P.; De Proft, F.; Langenaeker, W. Conceptual Density Functional Theory. Chem. Rev. 2003, 103, 1793– 1874, DOI: 10.1021/cr990029pGoogle Scholar138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXivFGgu7g%253D&md5=085c8ae5893c0b05158629e182ecb0a4Conceptual Density Functional TheoryGeerlings, P.; De Proft, F.; Langenaeker, W.Chemical Reviews (Washington, DC, United States) (2003), 103 (5), 1793-1873CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review on conceptual d. functional theory including the following topics: fundamental and computational aspects of DFT, DFT-based concepts and principles and applications of DFT.
- 139Geerlings, P.; Proft, F. D. Conceptual DFT: The Chemical Relevance of Higher Response Functions. Phys. Chem. Chem. Phys. 2008, 10, 3028– 3042, DOI: 10.1039/b717671fGoogle Scholar139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtVKmt7o%253D&md5=d0abd6b5a14679da7da2cef53918a636Conceptual DFT: the chemical relevance of higher response functionsGeerlings, P.; De Proft, F.Physical Chemistry Chemical Physics (2008), 10 (21), 3028-3042CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)A review. In recent years conceptual d. functional theory offered a perspective for the interpretation/prediction of exptl./theor. reactivity data on the basis of a series of response functions to perturbations in the no. of electrons and/or external potential. This approach has enabled the sharp definition and computation, from first principles, of a series of well-known but sometimes vaguely defined chem. concepts such as electronegativity and hardness. In this contribution, a short overview of the shortcomings of the simplest, first-order response functions is illustrated leading to a description of chem. bonding in a covalent interaction in terms of interacting atoms or groups, governed by electrostatics with the tendency to polarize bonds on the basis of electronegativity differences. The second order approach, well known until now, introduces the hardness/softness and Fukui function concepts related to polarizability and frontier MO theory, resp. The introduction of polarizability/softness is also considered in a historical perspective in which polarizability was, with some exceptions, mainly put forward in non covalent interactions. A particular series of response functions, arising when the changes in the external potential are solely provoked by changes in nuclear configurations (the "R-analogs") are also systematically considered. The main part of the contribution is devoted to third-order response functions which, at first sight, may be expected not to yield chem. significant information, as turns out to be for the hyperhardness. A counterexample is the dual descriptor and its R analog, the initial hardness response, which turns out to yield a firm basis to regain the Woodward-Hoffmann rules for pericyclic reactions based on a d.-only basis, i.e. without involving the phase, sign, symmetry of the wavefunction. Even the second-order nonlinear response functions are shown possibly to bear interesting information, e.g. on the local and global polarizability. Its derivs. may govern the influence of charge on the polarizability, the R-analogs being the nuclear Fukui function and the quadratic and cubic force consts. Although some of the higher order derivs. may be difficult to evaluate a comparison with the energy expansion used in spectroscopy in terms of nuclear displacements, nuclear magnetic moments, elec. and magnetic fields leads to the conjecture that, certainly cross terms may contain new, intricate information for understanding chem. reactivity.
- 140Proft, F. D.; Ayers, P. W.; Geerlings, P. The Chemical Bond; Wiley-Blackwell, 2014; pp 233– 270.
- 141Bergeler, M.; Simm, G. N.; Proppe, J.; Reiher, M. Heuristics-Guided Exploration of Reaction Mechanisms. J. Chem. Theory Comput. 2015, 11, 5712– 5722, DOI: 10.1021/acs.jctc.5b00866Google Scholar141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslCjtbjO&md5=c283427244c99d448f5c895d6f434b06Heuristics-Guided Exploration of Reaction MechanismsBergeler, Maike; Simm, Gregor N.; Proppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2015), 11 (12), 5712-5722CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)For the investigation of chem. reaction networks, the efficient and accurate detn. of all relevant intermediates and elementary reactions is mandatory. The complexity of such a network may grow rapidly, in particular if reactive species are involved that might cause a myriad of side reactions. Without automation, a complete investigation of complex reaction mechanisms is tedious and possibly unfeasible. Therefore, only the expected dominant reaction paths of a chem. reaction network (e.g., a catalytic cycle or an enzymic cascade) are usually explored in practice. Here, we present a computational protocol that constructs such networks in a parallelized and automated manner. Mol. structures of reactive complexes are generated based on heuristic rules derived from conceptual electronic-structure theory and subsequently optimized by quantum-chem. methods to produce stable intermediates of an emerging reaction network. Pairs of intermediates in this network that might be related by an elementary reaction according to some structural similarity measure are then automatically detected and subjected to an automated search for the connecting transition state. The results are visualized as an automatically generated network graph, from which a comprehensive picture of the mechanism of a complex chem. process can be obtained that greatly facilitates the anal. of the whole network. We apply our protocol to the Schrock dinitrogen-fixation catalyst to study alternative pathways of catalytic ammonia prodn.
- 142Gánti, T. Organization of Chemical Reactions into Dividing and Metabolizing Units: The Chemotons. BioSystems 1975, 7, 15– 21, DOI: 10.1016/0303-2647(75)90038-6
- 143Yandulov, D. V.; Schrock, R. R. Reduction of Dinitrogen to Ammonia at a Well-Protected Reaction Site in a Molybdenum Triamidoamine Complex. J. Am. Chem. Soc. 2002, 124, 6252– 6253, DOI: 10.1021/ja020186xGoogle Scholar143https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XjsVyhsb8%253D&md5=5a7abc5e8c8135193ceb83918f21ea43Reduction of Dinitrogen to Ammonia at a Well-Protected Reaction Site in a Molybdenum Triamidoamine ComplexYandulov, Dmitry V.; Schrock, Richard R.Journal of the American Chemical Society (2002), 124 (22), 6252-6253CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We have synthesized a triamidoamine ligand ([(RNCH2CH2)3N]3-) in which R is 3,5-(2,4,6-i-Pr3C6H2)2C6H3 (HexaIsoPropylTerphenyl or HIPT). The reaction between MoCl4(THF)2 and H3[HIPTN3N] in THF followed by 3.1 equiv of LiN(SiMe3)2 led to formation of orange [HIPTN3N]MoCl. Redn. of [HIPTN3N]MoCl with magnesium in THF under dinitrogen led to formation of salts that contain the {[HIPTN3N]Mo(N2)}- ion. The {[HIPTN3N]Mo(N2)}- ion can be oxidized by zinc chloride to give [HIPTN3N]Mo(N2) or protonated to give [HIPTN3N]Mo-N:N-H. Other relevant compds. that have been prepd. include {[HIPTN3N]Mo-N:NH2}+, [HIPTN3N]Mo≡N, {[HIPTN3N]Mo:NH}+, and {[HIPTN3N]Mo(NH3)}+. (The anion is usually {B(3,5-(CF3)2C6H3)4}- = {BAr'4}-.). Redn. of [HIPTN3N]Mo(N2) with CoCp2 in the presence of {2,6-lutidinium}BAr'4 in benzene leads to formation of ammonia and {[HIPTN3N]Mo(NH3)}+. Preliminary X-ray studies suggest that the HIPT substituent creates a deep, three-fold sym. cavity that protects a variety of dinitrogen redn. products against bimol. decompn. reactions, while at the same time the metal is left relatively open toward reactions near the equatorial amido ligands.
- 144Yandulov, D. V.; Schrock, R. R.; Rheingold, A. L.; Ceccarelli, C.; Davis, W. M. Synthesis and Reactions of Molybdenum Triamidoamine Complexes Containing Hexaisopropylterphenyl Substituents. Inorg. Chem. 2003, 42, 796– 813, DOI: 10.1021/ic020505lGoogle Scholar144https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjt1yqtg%253D%253D&md5=224f2e5ebc46cf53c66ce1e68f6de311Synthesis and Reactions of Molybdenum Triamidoamine Complexes Containing Hexaisopropylterphenyl SubstituentsYandulov, Dmitry V.; Schrock, Richard R.; Rheingold, Arnold L.; Ceccarelli, Christopher; Davis, William M.Inorganic Chemistry (2003), 42 (3), 796-813CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)The authors synthesized a triamidoamine ligand ([(RNCH2CH2)3N]3-) in which R is 3,5-(2,4,6-i-Pr3C6H2)2C6H3 (hexaisopropylterphenyl or HIPT). The reaction between MoCl4(THF)2 and H3[HIPTN3N] in THF followed by 3.1 equiv of LiN(SiMe3)2 gave orange [HIPTN3N]MoCl. Redn. of MoCl (Mo = [HIPTN3N]Mo) with Mg in THF under dinitrogen gave salts that contain the {Mo(N2)}- ion. The {Mo(N2)}- ion can be oxidized by ZnCl2 to give Mo(N2) or protonated to give MoN:NH. The latter decomps. to yield MoH. Other relevant compds. that were prepd. include {Mo:N-NH2}+ (by protonation of MoN:NH), Mo≡N, {Mo=NH}+ (by protonation of Mo≡N), and {Mo(NH3)}+ (by treating MoCl with NH3) (The anion is usually {B(3,5-(CF3)2C6H3)4}- = {BAr'4}-). X-ray studies were carried out on {Mg(DME)3}0.5[Mo(N2)], MoN:NMgBr(THF)3, Mo(N2), Mo≡N, and {Mo(NH3)}{BAr'4}. Probably the HIPT substituent on the triamidoamine ligand creates a cavity that stabilizes a variety of complexes that might be encountered in a hypothetical Chatt-like dinitrogen redn. scheme, perhaps largely by protecting against bimol. decompn. reactions.
- 145Eschenmoser, A.; Loewenthal, E. Chemistry of Potentially Prebiological Natural Products. Chem. Soc. Rev. 1992, 21, 1– 16, DOI: 10.1039/cs9922100001Google Scholar145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38Xht1egtL4%253D&md5=26e2c8a468693ecdbff4a3b01d3766beChemistry of potentially prebiological natural productsEschenmoser, Albert; Loewenthal, EliChemical Society Reviews (1992), 21 (1), 1-16CODEN: CSRVBR; ISSN:0306-0012.A review with 59 refs. on the title subject with regard to sugar phosphates, purines, pyrimidines and oligonucleotides.
- 146Delidovich, I. V.; Simonov, A. N.; Taran, O. P.; Parmon, V. N. Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective Synthesis. ChemSusChem 2014, 7, 1833– 1846, DOI: 10.1002/cssc.201400040Google Scholar146https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpslGjtLw%253D&md5=3f51d7aa82ef147a6e790097a698e7c5Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective SynthesisDelidovich, Irina V.; Simonov, Alexandr N.; Taran, Oxana P.; Parmon, Valentin N.ChemSusChem (2014), 7 (7), 1833-1846CODEN: CHEMIZ; ISSN:1864-5631. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The formose reaction (FR) was long the focus of intensive studies as a simple method for synthesis of complex biol. important monosaccharides and other sugar-like mols. from the simplest org. substrate-formaldehyde. The fundamental importance of the FR is predominantly connected with the ascertainment of plausible scenarios of chem. evolution which could occurred on the prebiotic Earth to produce the very first mols. of carbohydrates, amino- and nucleic acids, as well as other vitally important substances. The practical importance of studies on the FR is the elaboration of catalytic methods for the synthesis of rare and nonnatural monosaccharides and polyols. This Minireview considers the FR from the point of view of chemists working in the field of catalysis with emphasis on the mechanisms of numerous parallel and consequent catalytic transformations that take place during the FR. Based on its kinetics, the FR may be considered as a nonradical chain process with degenerate branching. The Minireview also considers different approaches to the control of selectivity of carbohydrate synthesis from formaldehyde and lower monosaccharides.
- 147Simm, G. N.; Reiher, M. Context-Driven Exploration of Complex Chemical Reaction Networks. J. Chem. Theory Comput. 2017, 13, 6108– 6119, DOI: 10.1021/acs.jctc.7b00945Google Scholar147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsleiurfJ&md5=1a898dab5d04f2c4889afb549a4dbb5aContext-Driven Exploration of Complex Chemical Reaction NetworksSimm, Gregor N.; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (12), 6108-6119CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The construction of a reaction network contg. all relevant intermediates and elementary reactions is necessary for the accurate description of chem. processes. In the case of a complex chem. reaction (involving, for instance, many reactants or highly reactive species), the size of such a network may grow rapidly. Here, we present a computational protocol that constructs such reaction networks in a fully automated fashion steered in an intuitive, graph-based fashion through a single graphical user interface. Starting from a set of initial reagents new intermediates are explored through intra- and intermol. reactions of already explored intermediates or new reactants presented to the network. This is done by assembling reactive complexes based on heuristic rules derived from conceptual electronic-structure theory and exploring the corresponding approx. reaction path. A subsequent path refinement leads to a min.-energy path which connects the new intermediate to the existing ones to form a connected reaction network. Tree traversal algorithms are then employed to detect reaction channels and catalytic cycles. We apply our protocol to the formose reaction to study different pathways of sugar formation and to rationalize its autocatalytic nature.
- 148Proppe, J.; Reiher, M. Mechanism Deduction from Noisy Chemical Reaction Networks. J. Chem. Theory Comput. 2018, submitted, [arXiv: 1803.09346].
- 149Husch, T.; Vaucher, A. C.; Reiher, M. Semiempirical Molecular Orbital Models based on the Neglect of Diatomic Differential Overlap Approximation. Int. J. Quantum Chem. 2018, e25799 DOI: 10.1002/qua.25799
- 150Husch, T.; Reiher, M. Comprehensive analysis of the neglect of diatomic differential overlap approximation. J. Chem. Theory Comput. 2018, 14, 5169– 5179, DOI: 10.1021/acs.jctc.8b00601Google Scholar150https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1KhtbzI&md5=1410f3e6922bfcc2d97eb12e6ebbb005Comprehensive Analysis of the Neglect of Diatomic Differential Overlap ApproximationHusch, Tamara; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (10), 5169-5179CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Many modern semiempirical MO models are built on the NDDO approxn. An in-depth understanding of this approxn. is therefore indispensable to rationalize the success of these semiempirical MO models and to develop further improvements on them. The NDDO approxn. provides a recipe to approx. electron-electron repulsion integrals (ERIs) in a sym. orthogonalized basis based on a far smaller no. of ERIs in a locally orthogonalized basis. We first analyze the NDDO approxn. by comparing ERIs in both bases for a selection of mols. and for a selection of basis sets. We find that the errors in Hartree-Fock and second-order Moller-Plesset perturbation theory energies grow roughly linearly with the no. of basis functions. We then examine different approaches to correct for the errors caused by the NDDO approxn. and propose a strategy to directly correct for them in the two-electron matrixes that enter the Fock operator.
- 151Simm, G. N.; Proppe, J.; Reiher, M. Error Assessment of Computational Models in Chemistry. Chimia 2017, 71, 202– 208, DOI: 10.2533/chimia.2017.202Google Scholar151https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1ajt7rK&md5=88488125dbc1ae5214a8b22d52d9570bError assessment of computational models in chemistrySimm, Gregor N.; Proppe, Jonny; Reiher, MarkusChimia (2017), 71 (4), 202-208CODEN: CHIMAD ISSN:. (Swiss Chemical Society)Computational models in chem. rely on a no. of approxns. The effect of such approxns. on observables derived from them is often unpredictable. Therefore, it is challenging to quantify the uncertainty of a computational result, which, however, is necessary to assess the suitability of a computational model. Common performance statistics such as the mean abs. error are prone to failure as they do not distinguish the explainable (systematic) part of the errors from their unexplainable (random) part. In this paper, we discuss problems and solns. for performance assessment of computational models based on several examples from the quantum chem. literature. For this purpose, we elucidate the different sources of uncertainty, the elimination of systematic errors, and the combination of individual uncertainty components to the uncertainty of a prediction.
- 152Proppe, J.; Reiher, M. Reliable Estimation of Prediction Uncertainty for Physicochemical Property Models. J. Chem. Theory Comput. 2017, 13, 3297– 3317, DOI: 10.1021/acs.jctc.7b00235Google Scholar152https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXpt1ykt7w%253D&md5=41bb917d7e3707ab9c6308a00dd056c9Reliable Estimation of Prediction Uncertainty for Physicochemical Property ModelsProppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (7), 3297-3317CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)One of the major challenges in computational science is to det. the uncertainty of a virtual measurement, that is the prediction of an observable based on calcns. As highly accurate first-principles calcns. are in general unfeasible for most phys. systems, one usually resorts to parameteric property models of observables, which require calibration by incorporating ref. data. The resulting predictions and their uncertainties are sensitive to systematic errors such as inconsistent ref. data, parametric model assumptions, or inadequate computational methods. Here, we discuss the calibration of property models in the light of bootstrapping, a sampling method that can be employed for identifying systematic errors and for reliable estn. of the prediction uncertainty. We apply bootstrapping to assess a linear property model linking the 57Fe Mossbauer isomer shift to the contact electron d. at the iron nucleus for a diverse set of 44 mol. iron compds. The contact electron d. is calcd. with 12 d. functionals across Jacob's ladder (PWLDA, BP86, BLYP, PW91, PBE, M06-L, TPSS, B3LYP, B3PW91, PBE0, M06, TPSSh). We provide systematic-error diagnostics and reliable, locally resolved uncertainties for isomer-shift predictions. Pure and hybrid d. functionals yield av. prediction uncertainties of 0.06-0.08 mm s-1 and 0.04-0.05 mm s-1, resp., the latter being close to the av. exptl. uncertainty of 0.02 mm s-1. Furthermore, we show that both model parameters and prediction uncertainty depend significantly on the compn. and no. of ref. data points. Accordingly, we suggest that rankings of d. functionals based on performance measures (e.g., the squared coeff. of correlation, r2, or the root-mean-square error, RMSE) should not be inferred from a single data set. This study presents the first statistically rigorous calibration anal. for theor. Mossbauer spectroscopy, which is of general applicability for physicochem. property models and not restricted to isomer-shift predictions. We provide the statistically meaningful ref. data set MIS39 and a new calibration of the isomer shift based on the PBE0 functional.
- 153Weymuth, T.; Proppe, J.; Reiher, M. Statistical Analysis of Semiclassical Dispersion Corrections. J. Chem. Theory Comput. 2018, 14, 2480– 2494, DOI: 10.1021/acs.jctc.8b00078Google Scholar153https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmvVaqsL4%253D&md5=723d9ba5398927668bdedd0141a9b508Statistical Analysis of Semiclassical Dispersion CorrectionsWeymuth, Thomas; Proppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (5), 2480-2494CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Semiclassical dispersion corrections developed by Grimme and co-workers have become indispensable in applications of Kohn-Sham d. functional theory. A deeper understanding of the underlying parametrization might be crucial for well-founded further improvements of this successful approach. To this end, we present an in-depth assessment of the fit parameters present in semiclassical (D3-type) dispersion corrections by means of a statistically rigorous anal. We find that the choice of the cost function generally has a small effect on the empirical parameters of D3-type dispersion corrections with respect to the ref. set under consideration. Only in a few cases, the choice of cost function has a surprisingly large effect on the total dispersion energies. In particular, the weighting scheme in the cost function can significantly affect the reliability of predictions. In order to obtain unbiased (data-independent) uncertainty ests. for both the empirical fit parameters and the corresponding predictions, we carried out a nonparametric bootstrap anal. This anal. reveals that the std. deviation of the mean of the empirical D3 parameters is small. Moreover, the mean prediction uncertainty obtained by bootstrapping is not much larger than previously reported error measures. On the basis of a jackknife anal., we find that the original ref. set is slightly skewed, but our results also suggest that this feature hardly affects the prediction of dispersion energies. Furthermore, we find that the introduction of small uncertainties to the ref. data does not change the conclusions drawn in this work. However, a rigorous anal. of error accumulation arising from different parametrizations reveals that error cancellation does not necessarily occur, leading to a monotonically increasing deviation in the dispersion energy with increasing mol. size. We discuss this issue in detail at the prominent example of the C60 "buckycatcher". We find deviations between individual parametrizations of several tens of kilocalories per mol in some cases. Hence, in combination with any calcn. of dispersion energies, we recommend to always det. the assocd. uncertainties for which we will provide a software tool.
- 154Proppe, J.; Husch, T.; Simm, G. N.; Reiher, M. Uncertainty quantification for quantum chemical models of complex reaction networks. Faraday Discuss. 2016, 195, 497– 520, DOI: 10.1039/C6FD00144KGoogle Scholar154https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFantbbF&md5=72ef620f8bd4517eb0c2c46fa32a05afUncertainty quantification for quantum chemical models of complex reaction networksProppe, Jonny; Husch, Tamara; Simm, Gregor N.; Reiher, MarkusFaraday Discussions (2016), 195 (Reaction Rate Theory), 497-520CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)A review. For the quant. understanding of complex chem. reaction mechanisms, it is, in general, necessary to accurately det. the corresponding free energy surface and to solve the resulting continuous-time reaction rate equations for a continuous state space. For a general (complex) reaction network, it is computationally hard to fulfill these two requirements. However, it is possible to approx. address these challenges in a phys. consistent way. On the one hand, it may be sufficient to consider approx. free energies if a reliable uncertainty measure can be provided. On the other hand, a highly resolved time evolution may not be necessary to still det. quant. fluxes in a reaction network if one is interested in specific time scales. In this paper, we present discrete-time kinetic simulations in discrete state space taking free energy uncertainties into account. The method builds upon thermo-chem. data obtained from electronic structure calcns. in a condensed-phase model. Our kinetic approach supports the anal. of general reaction networks spanning multiple time scales, which is here demonstrated for the example of the formose reaction. An important application of our approach is the detection of regions in a reaction network which require further investigation, given the uncertainties introduced by both approx. electronic structure methods and kinetic models. Such cases can then be studied in greater detail with more sophisticated first-principles calcns. and kinetic simulations.
- 155Simm, G.; Reiher, M. Error-Controlled Exploration of Chemical Reaction Networks with Gaussian Processes. J. Chem. Theory Comput. 2018, 14, 5238– 5248, DOI: 10.1021/acs.jctc.8b00504Google Scholar155https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1Gmt7vK&md5=116ed9b1481210ec5564eb6e1d0157f8Error-Controlled Exploration of Chemical Reaction Networks with Gaussian ProcessesSimm, Gregor N.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (10), 5238-5248CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)For a theor. understanding of the reactivity of complex chem. systems, relative energies of stationary points on potential energy hypersurfaces need to be calcd. to high accuracy. Due to the large no. of intermediates present in all but the simplest chem. processes, approx. quantum chem. methods are required that allow for fast evaluations of the relative energies but at the expense of accuracy. Despite the plethora of benchmark studies, the accuracy of a quantum chem. method is often difficult to assess. Moreover, a significant improvement of a method's accuracy (e.g., through reparameterization or systematic model extension) is rarely possible. Here, we present a new approach that allows for the systematic, problem-oriented, and rolling improvement of quantum chem. results through the application of Gaussian processes. Due to its Bayesian nature, reliable error ests. are provided for each prediction. A ref. method of high accuracy can be employed if the uncertainty assocd. with a particular calcn. is above a given threshold. The new data point is then added to a growing data set in order to continuously improve the model and, as a result, all subsequent predictions. Previous predictions are validated by the updated model to ensure that uncertainties remain within the given confidence bound, which we call backtracking. We demonstrate our approach with the example of a complex chem. reaction network.
- 156Lagorce, D.; Pencheva, T.; Villoutreix, B. O.; Miteva, M. A. DG-AMMOS: A New Tool to Generate 3D Conformation of Small Molecules Using Distance Geometry and Automated Molecular Mechanics Optimization for in Silico Screening. BMC Chem. Biol. 2009, 9, 6, DOI: 10.1186/1472-6769-9-6Google Scholar156https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjnsVKrtA%253D%253D&md5=6722e659d6b334955fbc5239df28e37fDG-AMMOS: a new tool to generate 3d conformation of small molecules using distance geometry and automated molecular mechanics optimization for in silico screeningLagorce David; Villoutreix Bruno O; Miteva Maria A; Pencheva TaniaBMC chemical biology (2009), 9 (), 6 ISSN:.BACKGROUND: Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. RESULTS: Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. CONCLUSION: DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.
- 157Riniker, S.; Landrum, G. A. Better Informed Distance Geometry: Using What We Know To Improve Conformation Generation. J. Chem. Inf. Model. 2015, 55, 2562– 2574, DOI: 10.1021/acs.jcim.5b00654Google Scholar157https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVeqsrjP&md5=8ee6d7d1999924fc2b42f76577f8ec51Better Informed Distance Geometry: Using What We Know To Improve Conformation GenerationRiniker, Sereina; Landrum, Gregory A.Journal of Chemical Information and Modeling (2015), 55 (12), 2562-2574CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Small org. mols. are often flexible, i.e., they can adopt a variety of low-energy conformations in soln. that exist in equil. with each other. Two main search strategies are used to generate representative conformational ensembles for mols.: systematic and stochastic. In the first approach, each rotatable bond is sampled systematically in discrete intervals, limiting its use to mols. with a small no. of rotatable bonds. Stochastic methods, however, sample the conformational space of a mol. randomly and can thus be applied to more flexible mols. Different methods employ different degrees of exptl. data for conformer generation. So-called knowledge-based methods use predefined libraries of torsional angles and ring conformations. In the distance geometry approach, however, a smaller amt. of empirical information was used, i.e., ideal bond lengths, ideal bond angles, and a few ideal torsional angles. Distance geometry is a computationally fast method to generate conformers, but it has the downside that purely distance-based constraints tend to lead to distorted arom. rings and sp2 centers. To correct this, the resulting conformations are often minimized with a force field, adding computational complexity and run time. Here the authors present an alternative strategy that combines the distance geometry approach with exptl. torsion-angle preferences obtained from small-mol. crystallog. data. The torsional angles are described by a previously developed set of hierarchically structured SMARTS patterns. The new approach is implemented in the open-source cheminformatics library RDKit, and its performance is assessed by comparing the diversity of the generated ensemble and the ability to reproduce crystal conformations taken from the crystal structures of small mols. and protein-ligand complexes.
- 158Vainio, M. J.; Johnson, M. S. Generating Conformer Ensembles Using a Multiobjective Genetic Algorithm. J. Chem. Inf. Model. 2007, 47, 2462– 2474, DOI: 10.1021/ci6005646Google Scholar158https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtVOnsL7L&md5=e621e6eedf3d93ff6236bc4887f25e35Generating Conformer Ensembles Using a Multiobjective Genetic AlgorithmVainio, Mikko J.; Johnson, Mark S.Journal of Chemical Information and Modeling (2007), 47 (6), 2462-2474CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The task of generating a nonredundant set of low-energy conformations for small mols. is of fundamental importance for many mol. modeling and drug-design methodologies. Several approaches to conformer generation have been published. Exhaustive searches suffer from the exponential growth of the search space with increasing degrees of conformational freedom (no. of rotatable bonds). Stochastic algorithms do not suffer as much from the exponential increase of search space and provide a good coverage of the energy min. Here, the use of a multiobjective genetic algorithm in the generation of conformer ensembles is investigated. Distance geometry is used to generate an initial conformer, which is then subject to geometric modifications encoded by the individuals of the genetic algorithm. The geometric modifications apply to torsion angles about rotatable bonds, stereochem. of double bonds and tetrahedral chiral centers, and ring conformations. The geometric diversity of the evolving conformer ensemble is preserved by a fitness-sharing mechanism based on the root-mean-square distance of the at. coordinates. Mol. symmetry is taken into account in the distance calcn. The geometric modifications introduce strain into the structures. The strain is relaxed using an MMFF94-like force field in a postprocessing step that also removes conformational duplicates and structures whose strain energy remains above a predefined window from the min. energy value found in the set. The implementation, called Balloon, is available free of charge on the Internet (http://www.abo.fi/∼mivainio/balloon/).
- 159Leite, T. B.; Gomes, D.; Miteva, M. A.; Chomilier, J.; Villoutreix, B. O.; Tufféry, P. Frog: A FRee Online druG 3D Conformation Generator. Nucleic Acids Res. 2007, 35, W568– W572, DOI: 10.1093/nar/gkm289
- 160Miteva, M. A.; Guyon, F.; Tufféry, P. Frog2: Efficient 3D Conformation Ensemble Generator for Small Compounds. Nucleic Acids Res. 2010, 38, W622– W627, DOI: 10.1093/nar/gkq325Google Scholar160https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXotVSqsr8%253D&md5=ec1c9860de9eb1e81e9e8d81f24f550bFrog2: Efficient 3D conformation ensemble generator for small compoundsMiteva, Maria A.; Guyon, Frederic; Tuffery, PierreNucleic Acids Research (2010), 38 (Web Server), W622-W627CODEN: NARHAD; ISSN:0305-1048. (Oxford University Press)Frog is a web tool dedicated to small compd. 3D generation. Here we present the new version, Frog2, which allows the generation of conformation ensembles of small mols. starting from either 1D, 2D or 3D description of the compds. From a compd. description in one of the SMILES, SDF or mol2 formats, the server will return an ensemble of diverse conformers generated using a two stage Monte Carlo approach in the dihedral space. When starting from 1D or 2D description of compds., Frog2 is capable to detect the sites of ambiguous stereoisomery, and thus to sample different stereoisomers. Frog2 also embeds new energy minimization and ring generation facilities that solve the problem of some missing cycle structures in the Frog1 ring library. Finally, the optimized generator of conformation ensembles in Frog2 results in a gain of computational time permitting Frog2 to be up to 20 times faster that Frog1, while producing satisfactory conformations in terms of structural quality and conformational diversity. The high speed and the good quality of generated conformational ensembles makes it possible the treatment of larger compd. collections using Frog2. The server and documentation are freely available at http://bioserv.rpbs.univ-paris-diderot.fr/Frog2.
- 161Hawkins, P. C. D.; Skillman, A. G.; Warren, G. L.; Ellingson, B. A.; Stahl, M. T. Conformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural Database. J. Chem. Inf. Model. 2010, 50, 572– 584, DOI: 10.1021/ci100031xGoogle Scholar161https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjtlaisrY%253D&md5=fb87ecc9c51eddef63b41fffcd9babeeConformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural DatabaseHawkins, Paul C. D.; Skillman, A. Geoffrey; Warren, Gregory L.; Ellingson, Benjamin A.; Stahl, Matthew T.Journal of Chemical Information and Modeling (2010), 50 (4), 572-584CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Here, we present the algorithm and validation for OMEGA, a systematic, knowledge-based conformer generator. The algorithm consists of three phases: assembly of an initial 3D structure from a library of fragments; exhaustive enumeration of all rotatable torsions using values drawn from a knowledge-based list of angles, thereby generating a large set of conformations; and sampling of this set by geometric and energy criteria. Validation of conformer generators like OMEGA has often been undertaken by comparing computed conformer sets to exptl. mol. conformations from crystallog., usually from the Protein Databank (PDB). Such an approach is fraught with difficulty due to the systematic problems with small mol. structures in the PDB. Methods are presented to identify a diverse set of small mol. structures from cocomplexes in the PDB that has maximal reliability. A challenging set of 197 high quality, carefully selected ligand structures from well-solved models was obtained using these methods. This set will provide a sound basis for comparison and validation of conformer generators in the future. Validation results from this set are compared to the results using structures of a set of druglike mols. extd. from the Cambridge Structural Database (CSD). OMEGA is found to perform very well in reproducing the crystallog. conformations from both these data sets using two complementary metrics of success.
- 162Schärfer, C.; Schulz-Gasch, T.; Hert, J.; Heinzerling, L.; Schulz, B.; Inhester, T.; Stahl, M.; Rarey, M. CONFECT: Conformations from an Expert Collection of Torsion Patterns. ChemMedChem 2013, 8, 1690– 1700, DOI: 10.1002/cmdc.201300242Google Scholar162https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3sfotVymtA%253D%253D&md5=9aed22ca5ec1872aea505dadb9d99baeCONFECT: conformations from an expert collection of torsion patternsScharfer Christin; Schulz-Gasch Tanja; Hert Jerome; Heinzerling Lennart; Schulz Benjamin; Inhester Therese; Stahl Martin; Rarey MatthiasChemMedChem (2013), 8 (10), 1690-700 ISSN:.The generation of sets of low-energy conformations for a given molecule is a central task in drug design. Herein we present a new conformation generator called CONFECT that builds on our previously published library of torsion patterns. Conformations are generated as well as ranked by means of normalized frequency distributions derived from the Cambridge Structural Database (CSD). Following an incremental construction approach, conformations are selected from a systematic enumeration within energetic boundaries. The new tool is benchmarked in several different ways, indicating that it allows the efficient generation of high-quality conformation ensembles. These ensembles are smaller than those produced by state-of-the-art tools, yet they effectively cover conformational space.
- 163Guba, W.; Meyder, A.; Rarey, M.; Hert, J. Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small Molecules. J. Chem. Inf. Model. 2016, 56, 1– 5, DOI: 10.1021/acs.jcim.5b00522Google Scholar163https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XovFKjsA%253D%253D&md5=0e26d363bad3069851a04bf977027f53Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small MoleculesGuba, Wolfgang; Meyder, Agnes; Rarey, Matthias; Hert, JeromeJournal of Chemical Information and Modeling (2016), 56 (1), 1-5CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The Torsion Library contains hundreds of rules for small mol. conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by mol. design experts. The torsion rules are encoded as SMARTS patterns and categorize rotatable bonds via a traffic light coloring scheme. We have systematically revised all torsion rules to better identify highly strained conformations and minimize the no. of false alerts for CSD small mol. X-ray structures. For this new release, we added or substantially modified 78 torsion patterns and reviewed all angles and tolerance intervals. The overall no. of red alerts for a filtered CSD data set with 130 000 structures was reduced by a factor of 4 compared to the predecessor. This is of clear advantage in 3D virtual screening where hits should only be removed by a conformational filter if they are in energetically inaccessible conformations.
- 164Batter, J.; Brooks, F. GROPE-I: A Computer Display to the Sense of Feel. Proceedings of the International Federation of Information Processing 1971, 759– 763Google ScholarThere is no corresponding record for this reference.
- 165Noll, A. M. Man-Machine Tactile Communication. J. Soc. Inform. Dis. 1972, 6–11, 30Google ScholarThere is no corresponding record for this reference.
- 166Atkinson, W. D.; Bond, K. E.; Tribble, G. L.; Wilson, K. R. Computing with Feeling. Comp. and Graph. 1977, 2, 97– 103, DOI: 10.1016/0097-8493(77)90009-7
- 167Lancaster, S. J. Immersed in virtual molecules. Nature Rev. Chem. 2018, 2, 253– 254, DOI: 10.1038/s41570-018-0043-5Google Scholar167https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvVKnsb3M&md5=886aaa061e23d04e29d0b2bdc99df026Immersed in virtual moleculesLancaster, Simon J.Nature Reviews Chemistry (2018), 2 (10), 253-254CODEN: NRCAF7; ISSN:2397-3358. (Nature Research)A full grasp of chem. requires students to be able to connect microscopic reality with symbolic representations. Immersive virtual reality provides a soln. for those who need a tangible link between these representations.
- 168Aspuru-Guzik, A.; Lindh, R.; Reiher, M. The Matter (R)evolution. ACS Cent. Sci. 2018, 4, 144– 152, DOI: 10.1021/acscentsci.7b00550Google Scholar168https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitF2gsrk%253D&md5=b606a11b4272d62ae4f7de4b7709d25aThe Matter Simulation (R)evolutionAspuru-Guzik, Alan; Lindh, Roland; Reiher, MarkusACS Central Science (2018), 4 (2), 144-152CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)To date, the program for the development of methods and models for atomistic and continuum simulation directed toward chems. and materials has reached an incredible degree of sophistication and maturity. Currently, one can witness an increasingly rapid emergence of advances in computing, artificial intelligence, and robotics. This drives us to consider the future of computer simulation of matter from the mol. to the human length and time scales in a radical way that deliberately dares to go beyond the foreseeable next steps in any given discipline. This perspective article presents a view on this future development that we believe is likely to become a reality during our lifetime.
- 169Matthews, D. Science goes virtual. Nature 2018, 557, 127– 128, DOI: 10.1038/d41586-018-04997-2
- 170Cruz-Neira, C.; Sandin, D. J.; DeFanti, T. A. Surround-Screen Projection-Based Virtual Reality: The Design and Implementation of the CAVE. Proceedings of the 20th Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, NY, USA, 1993; pp 135– 142.
- 171Ai, Z.; Fröhlich, T. Molecular Dynamics Simulation in Virtual Environments. Comput. Graphics Forum 1998, 17, 267– 273, DOI: 10.1111/1467-8659.00273
- 172Prins, J. F.; Hermans, J.; Mann, G.; Nyland, L. S.; Simons, M. A Virtual Environment for Steered Molecular Dynamics. Future Gener. Comp. Sy. 1999, 15, 485– 495, DOI: 10.1016/S0167-739X(99)00005-9
- 173Ǩrenek, A. Haptic Rendering of Complex Force Fields. Proceedings of the Workshop on Virtual Environments 2003; ACM: New York, NY, USA, 2003; pp 231– 239.
- 174Lee, Y.-G.; Lyons, K. W. Smoothing Haptic Interaction Using Molecular Force Calculations. Comput.-Aided Design 2004, 36, 75– 90, DOI: 10.1016/S0010-4485(03)00080-0
- 175Morin, S.; Redon, S. A Force-Feedback Algorithm for Adaptive Articulated-Body Dynamics Simulation. IEEE International Conference on Robotics and Automation; IEEE, 2007; pp 3245– 3250.
- 176Daunay, B.; Régnier, S. Stable Six Degrees of Freedom Haptic Feedback for Flexible Ligand-Protein Docking. Comput.-Aided Design 2009, 41, 886– 895, DOI: 10.1016/j.cad.2009.06.010
- 177Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Haptic Feedback for Molecular Simulation. 2009 IEEE/RSJ. International Conference on Intelligent Robots and Systems; IEEE, 2009; pp 237– 242.
- 178Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Comparing Position and Force Control for Interactive Molecular Simulators with Haptic Feedback. J. Mol. Graphics Modell. 2010, 29, 280– 289, DOI: 10.1016/j.jmgm.2010.06.003Google Scholar178https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtFamtLvP&md5=8d81e29d4693725c0ada3ce7db0cebc0Comparing position and force control for interactive molecular simulators with haptic feedbackBolopion, Aude; Cagneau, Barthelemy; Redon, Stephane; Regnier, StephaneJournal of Molecular Graphics & Modelling (2010), 29 (2), 280-289CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)This paper presents a novel tool for the anal. of new mol. structures which enables a wide variety of manipulations. It is composed of a mol. simulator and a haptic device. The simulation software deals with systems of hundreds or thousands of degrees of freedom and computes the reconfiguration of the mols. in a few tenths of a second. For the ease of manipulation and to help the operator understand nanoscale phenomena, a haptic device is connected to the simulator. To handle a wide variety of applications, both position and force control are implemented. To our knowledge, this is the first time the applications of force control are detailed for mol. simulation. These two control modes are compared in terms of adequacy with mol. dynamics, transparency and stability sensitivity with respect to environmental conditions. Based on their specificity the operations they can realize are detailed. Expts. highlight the usability of our tool for the different steps of the anal. of mol. structures. It includes the global reconfiguration of a mol. system, the measurement of mol. properties and the comprehension of nanoscale interactions. Compared to most existing systems, the one developed in this paper offers a wide range of possible expts. The detailed anal. of the properties of the control modes can be easily used to implement haptic feedback on other mol. simulators.
- 179Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Haptic Molecular Simulation Based on Force Control. 2010 IEEE/ASME International Conference on Advanced Intelligent Mechatronics; IEEE, 2010; pp 329– 334.
- 180Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Variable Gain Haptic Coupling for Molecular Simulation. 2011 IEEE World Haptics Conference; IEEE, 2011; pp 469– 474.
- 181Durlach, N.; Mavor, A.; Development, C.; Board, C.; Council, N. Virtual Reality: Scientific and Technological Challenges; National Academies Press, 1994.Google ScholarThere is no corresponding record for this reference.
- 182Mark, W. R.; Randolph, S. C.; Finch, M.; Van Verth, J. M.; Taylor, R. M., II. Adding Force Feedback to Graphics Systems: Issues and Solutions. Proceedings of the 23rd Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, 1996; pp 447– 452.
- 183Ruspini, D. C.; Kolarov, K.; Khatib, O. The Haptic Display of Complex Graphical Environments. Proceedings of the 24th Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, 1997; pp 345– 352.
- 184Cruz-Neira, C.; Langley, R.; Bash, P. VIBE: A Virtual Biomolecular Environment for Interactive Molecular Modeling. Comput. Chem. 1996, 20, 469– 477, DOI: 10.1016/0097-8485(96)00009-5Google Scholar184https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XlslWhu7Y%253D&md5=c1c2ca7665c30f7500d6b2e721dc29e0VIBE: a virtual biomolecular environment for interactive molecular modelingCruz-Neira, C.; Langley, R.; Bash, P. A.Computers & Chemistry (Oxford) (1996), 20 (4), 469-477CODEN: COCHDK; ISSN:0097-8485. (Elsevier)Virtual reality tightly coupled to high performance computing and communications ushers in a new era for the study of mol. recognition and the rational design of pharmaceutical compds. We have created a Virtual Biomol. Environment (VIBE), which consists of (1) massively parallel computing to simulate the phys. and chem. properties of a mol. system, (2) the Cave Automatic Virtual Environment (CAVE) for immersive display and interaction with the mol. system, and (3) a high-speed network interface to exchange data between the simulation and the CAVE. VIBE enables mol. scientists to have a visual, auditory, and haptic experience with a chem. system, while simultaneously manipulating its phys. properties by steering, in real-time, a simulation executed on a supercomputer. We demonstrate the characteristics of VIBE using a HIV protease-cyclic urea inhibitor complex.
- 185Férey, N.; Nelson, J.; Martin, C.; Picinali, L.; Bouyer, G.; Tek, A.; Bourdot, P.; Burkhardt, J.; Katz, B.; Ammi, M.; Etchebest, C.; Autin, L. Multisensory VR Interaction for Protein-Docking in the CoRSAIRe Project. Virtual Reality 2009, 13, 273– 293, DOI: 10.1007/s10055-009-0136-z
- 186Glowacki, D. R.; O’Connor, M.; Calabro, G.; Price, J.; Tew, P.; Mitchell, T.; Hyde, J.; Tew, D. P.; Coughtrie, D. J.; McIntosh-Smith, S. A GPU-Accelerated Immersive Audio-Visual Framework for Interaction with Molecular Dynamics Using Consumer Depth Sensors. Faraday Discuss. 2014, 169, 63– 87, DOI: 10.1039/C4FD00008K
- 187Arbon, R. E.; Jones, A. J.; Bratholm, L. A.; Mitchell, T.; Glowacki, D. R. Sonifying Stochastic Walks on Biomolecular Energy Landscapes. 2018, arXiv 1803.05805.Google ScholarThere is no corresponding record for this reference.
- 188Ouh-young, M.; Pique, M.; Hughes, J.; Srinivasan, N.; Brooks, F. P. Using a Manipulator for Force Display in Molecular Docking. IEEE International Conference on Robotics and Automation; IEEE, 1988; pp 1824– 1829.
- 189Brooks, F. P., Jr.; Ouh-Young, M.; Batter, J. J.; Jerome Kilpatrick, P. Project GROPE — Haptic Displays for Scientific Visualization. SIGGRAPH Comput. Graph. 1990, 24, 177– 185, DOI: 10.1145/97880.97899
- 190Levine, D.; Facello, M.; Hallstrom, P.; Reeder, G.; Walenz, B.; Stevens, F. Stalk: An Interactive System for Virtual Molecular Docking. IEEE Comput. Sci. Eng. 1997, 4, 55– 65, DOI: 10.1109/99.609834Google Scholar190https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXkslOksro%253D&md5=13346f7b2c9a5751e55e859fea6dc97dStalk: an interactive system for virtual molecular dockingLevine, David; Facello, Michael; Hallstrom, Philip; Reeder, Gregory; Walenz, Brian; Stevens, FredIEEE Computational Science & Engineering (1997), 4 (2), 55-65CODEN: ISCEE4; ISSN:1070-9924. (IEEE Computer Society)Several recent technols., i.e., genetic algorithms, parallel and distributed computing, virtual reality, and high-speed networking, underlie a new approach to the computational study of how biomols. interact or dock together. With the Stalk system, a user in a virtual reality environment can interact with a genetic algorithm running on a parallel computer to help in the search for likely geometric configurations.
- 191Brooks, F. P., Jr. Impressions by a dinosaur. Faraday Discuss. 2014, 169, 521– 527, DOI: 10.1039/C4FD00130C
- 192O’Connor, M.; Deeks, H. M.; Dawn, E.; Metatla, O.; Roudaut, A.; Sutton, M.; Thomas, L. M.; Glowacki, B. R.; Sage, R.; Tew, P.; Wonnacott, M.; Bates, P.; Mulholland, A. J.; Glowacki, D. R. Sampling Molecular Conformations and Dynamics in a Multiuser Virtual Reality Framework. Sci. Adv. 2018, 4, eaat2731 DOI: 10.1126/sciadv.aat2731
- 193Bayazit, O.; Song, G.; Amato, N. Ligand Binding with OBPRM and User Input. IEEE International Conference on Robotics and Automation; IEEE, 2001; pp 954– 959.
- 194Nagata, H.; Mizushima, H.; Tanaka, H. Concept and Prototype of Protein-Ligand Docking Simulator with Force Feedback Technology. Bioinformatics 2002, 18, 140– 146, DOI: 10.1093/bioinformatics/18.1.140
- 195Lai-Yuen, S. K.; Lee, Y.-S. Computer-Aided Molecular Design (CAMD) with Force-Torque Feedback. Ninth International Conference on Computer Aided Design and Computer Graphics; ACM: New York, 2005; pp 199– 204.
- 196Birmanns, S.; Wriggers, W. Interactive Fitting Augmented by Force-Feedback and Virtual Reality. J. Struct. Biol. 2003, 144, 123– 131, DOI: 10.1016/j.jsb.2003.09.018
- 197Wollacott, A. M.; Merz, K. M., Jr. Haptic Applications for Molecular Structure Manipulation. J. Mol. Graphics Modell. 2007, 25, 801– 805, DOI: 10.1016/j.jmgm.2006.07.005Google Scholar197https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsFOiu7w%253D&md5=53a6dc20d08d1a0de0cee9053589ddf9Haptic applications for molecular structure manipulationWollacott, Andrew M.; Merz, Kenneth M.Journal of Molecular Graphics & Modelling (2007), 25 (6), 801-805CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Inc.)We describe the application of haptic technol. to enhance the information available in chem. systems, specifically related to computational drug design. These methods are designed to build upon the visual information presented by mol. viewers and add the sensation of touch, or force feedback. The addn. of sensory input can aid in the anal. of mol. structures and the understanding of intermol. interactions by delivering chem. relevant forces to the end user.
- 198Subasi, E.; Basdogan, C. A New Haptic Interaction and Visualization Approach for Rigid Molecular Docking in Virtual Environments. Presence 2008, 17, 73– 90, DOI: 10.1162/pres.17.1.73
- 199Heyd, J.; Birmanns, S. Immersive Structural Biology: A New Approach to Hybrid Modeling of Macromolecular Assemblies. Virtual Reality 2009, 13, 245– 255, DOI: 10.1007/s10055-009-0129-y
- 200Anthopoulos, A.; Pasqualetto, G.; Grimstead, I.; Brancale, A. Haptic-Driven, Interactive Drug Design: Implementing a GPU-Based Approach to Evaluate the Induced Fit Effect. Faraday Discuss. 2014, 169, 323– 342, DOI: 10.1039/C3FD00139CGoogle Scholar200https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7jE&md5=baa69798111ce24fac6a771e906d262eHaptic-driven, interactive drug design: implementing a GPU-based approach to evaluate the induced fit effectAnthopoulos, Athanasios; Pasqualetto, Gaia; Grimstead, Ian; Brancale, AndreaFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 323-342CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)In this paper, we describe a hybrid meta-heuristics method of energy minimization and conformational sampling and its application into our haptic-driven mol. modeling simulator. The proposed method has been designed to suit real-time mol. docking simulations, where the time-lapse between two successive ligand poses is relatively small. In these situations, the energy minimization problem becomes increasingly complex and chaotic. The algorithm is tuned to take advantage of recent advances in GPU computing with asynchronous kernel execution, which has allowed us to include full protein flexibility in the real-time interactive, haptic-driven simulations. Finally, in this paper, we will also discuss the implementation of such high-performance computing approaches in our software, discussing the results of our initial validation studies, highlighting the advantages and limitations of such interactive methodol.
- 201Iakovou, G.; Hayward, S.; Laycock, S. D. A Real-Time Proximity Querying Algorithm for Haptic-Based Molecular Docking. Faraday Discuss. 2014, 169, 359– 377, DOI: 10.1039/C3FD00123GGoogle Scholar201https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7jP&md5=ba322c73d491c8d3218f2ec2e97f4a3fA real-time proximity querying algorithm for haptic-based molecular dockingIakovou, Georgios; Hayward, Steven; Laycock, StephenFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 359-377CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Intermol. binding underlies every metabolic and regulatory processes of the cell, and the therapeutic and pharmacol. properties of drugs. Mol. docking systems model and simulate these interactions in silico and allow us to study the binding process. Haptic-based docking provides an immersive virtual docking environment where the user can interact with and guide the mols. to their binding pose. Moreover, it allows human perception, intuition and knowledge to assist and accelerate the docking process, and reduces incorrect binding poses. Crucial for interactive docking is the real-time calcn. of interaction forces. For smooth and accurate haptic exploration and manipulation, force-feedback cues have to be updated at a rate of 1 kHz. Hence, force calcns. must be performed within 1ms. To achieve this, modern haptic-based docking approaches often utilize pre-computed force grids and linear interpolation. However, such grids are time-consuming to pre-compute (esp. for large mols.), memory hungry, can induce rough force transitions at cell boundaries and cannot be applied to flexible docking. Here we propose an efficient proximity querying method for computing intermol. forces in real time. Our motivation is the eventual development of a haptic-based docking soln. that can model mol. flexibility. Uniquely in a haptics application we use octrees to decomp. the 3D search space in order to identify the set of interacting atoms within a cut-off distance. Force calcns. are then performed on this set in real time. The implementation constructs the trees dynamically, and computes the interaction forces of large mol. structures (i.e. consisting of thousands of atoms) within haptic refresh rates. We have implemented this method in an immersive, haptic-based, rigid-body, mol. docking application called Haptimol_RD. The user can use the haptic device to orientate the mols. in space, sense the interaction forces on the device, and guide the mols. to their binding pose. Haptimol_RD is designed to run on consumer level hardware, i.e. there is no need for specialized/proprietary hardware.
- 202Iakovou, G.; Hayward, S.; Laycock, S. D. Adaptive GPU-Accelerated Force Calculation for Interactive Rigid Molecular Docking Using Haptics. J. Mol. Graphics Modell. 2015, 61, 1– 12, DOI: 10.1016/j.jmgm.2015.06.003Google Scholar202https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtF2ksbzL&md5=fc7fcb1082a8e50b08323d4ab720b249Adaptive GPU-accelerated force calculation for interactive rigid molecular docking using hapticsIakovou, Georgios; Hayward, Steven; Laycock, Stephen D.Journal of Molecular Graphics & Modelling (2015), 61 (), 1-12CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)Mol. docking systems model and simulate in silico the interactions of intermol. binding. Haptics-assisted docking enables the user to interact with the simulation via their sense of touch, but a stringent time constraint on the computation of forces is imposed due to the sensitivity of the human haptic system. To simulate high fidelity smooth and stable feedback the haptic feedback loop should run at rates of 500 Hz to 1 kHz. The authors present an adaptive force calcn. approach that can be executed in parallel on a wide range of Graphics Processing Units (GPUs) for interactive haptics-assisted docking with wider applicability to mol. simulations. Prior to the interactive session either a regular grid or an octree is selected according to the available GPU memory to det. the set of interat. interactions within a cutoff distance. The total force is then calcd. from this set. The approach can achieve force updates in <2 ms for mol. structures comprising hundreds of thousands of atoms each, with performance improvements of up to 90 times the speed of current CPU-based force calcn. approaches used in interactive docking. Furthermore, it overcomes several computational limitations of previous approaches such as pre-computed force grids, and could potentially be used to model receptor flexibility at haptic refresh rates.
- 203Iakovou, G.; Hayward, S.; Laycock, S. D. Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with Haptics. J. Chem. Inf. Model. 2017, 57, 1142– 1152, DOI: 10.1021/acs.jcim.7b00051Google Scholar203https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmsVahs74%253D&md5=88a043fa234a92e12c81dfd453884b01Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with HapticsIakovou, Georgios; Hayward, Steven; Laycock, Stephen D.Journal of Chemical Information and Modeling (2017), 57 (5), 1142-1152CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Haptic technol. facilitates user interaction with the virtual world via the sense of touch. In mol. docking, haptics enables the user to sense the interaction forces during the docking process. Here the authors describe a haptics-assisted interactive software tool, called Haptimol_RD, for the study of docking interactions. By utilizing GPU-accelerated proximity querying methods very large systems can now be studied. Methods for force scaling, multipoint collision response and haptic navigation are described that address force stability issues that are particular to the interactive docking of large systems. Thus, Haptimol_RD expands, for the first time, the use of interactive biomol. haptics to the study of protein-protein interactions. Unlike existing approaches, Haptimol_RD is designed to run on relatively inexpensive consumer-level hardware and is freely available to the community.
- 204Izrailev, S.; Stepaniants, S.; Isralewitz, B.; Kosztin, D.; Lu, H.; Molnar, F.; Wriggers, W.; Schulten, K. In Computational Molecular Dynamics: Challenges, Methods, Ideas; Deuflhard, P., Hermans, J., Leimkuhler, B., Mark, A., Reich, S., Skeel, R., Eds.; Lecture Notes in Computational Science and Engineering; Springer: Berlin, Heidelberg, 1999; Vol. 4, pp 39– 65.
- 205Grubmüller, H.; Heymann, B.; Tavan, P. Ligand Binding: Molecular Mechanics Calculation of the Streptavidin-Biotin Rupture Force. Science 1996, 271, 997– 999, DOI: 10.1126/science.271.5251.997Google Scholar205https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XhtFCru7g%253D&md5=8a013b443101d48aed80fcde1ec7d924Ligand binding: molecular mechanics calculation of the streptavidin-biotin rupture forceGrubmueller, Helmut; Heymann, Berthold; Tavan, PaulScience (Washington, D. C.) (1996), 271 (5251), 997-9CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The force required to rupture the streptavidin-biotin complex was calcd. here by computer simulations. The computed force agrees well with that obtained by recent single mol. at. force microscope expts. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, addnl. water bridges substantially enhance the stability of the complex and even dominate the binding interactions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were obsd.
- 206Izrailev, S.; Stepaniants, S.; Balsera, M.; Oono, Y.; Schulten, K. Molecular Dynamics Study of Unbinding of the Avidin-Biotin Complex. Biophys. J. 1997, 72, 1568– 1581, DOI: 10.1016/S0006-3495(97)78804-0Google Scholar206https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXitFeisbk%253D&md5=649ad913ebac2d1b320aebef229a8c50Molecular dynamics study of unbinding of the avidin-biotin complexIzrailev, S.; Stepaniants, S.; Balsera, M.; Oono, Y.; Schulten, K.Biophysical Journal (1997), 72 (4), 1568-1581CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)We report mol. dynamics simulations that induce, over periods of 40-500 ps, the unbinding of biotin from avidin by means of external harmonic forces with force consts. close to those of AFM cantilevers. The applied forces are sufficiently large to reduce the overall binding energy enough to yield unbinding within the measurement time. Our study complements earlier work on biotin-streptavidin that employed a much larger harmonic force const. The simulations reveal a variety of unbinding pathways, the role of key residues contributing to adhesion as well as the spatial range over which avidin binds biotin. In contrast to the previous studies, the calcd. rupture forces exceed by far those obsd. We demonstrate, in the framework of models expressed in terms of one-dimensional Langevin equations with a schematic binding potential, the assocd. Smoluchowski equations, and the theory of first passage times, that picosecond to nanosecond simulation of ligand unbinding requires such strong forces that the resulting protein-ligand motion proceeds far from the thermally activated regime of millisecond AFM expts., and that simulated unbinding cannot be readily extrapolated to the exptl. obsd. rupture.
- 207Balsera, M.; Stepaniants, S.; Izrailev, S.; Oono, Y.; Schulten, K. Reconstructing Potential Energy Functions from Simulated Force-Induced Unbinding Processes. Biophys. J. 1997, 73, 1281– 1287, DOI: 10.1016/S0006-3495(97)78161-X
- 208Isralewitz, B.; Izrailev, S.; Schulten, K. Binding Pathway of Retinal to Bacterio-Opsin: A Prediction by Molecular Dynamics Simulations. Biophys. J. 1997, 73, 2972– 2979, DOI: 10.1016/S0006-3495(97)78326-7Google Scholar208https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXnsl2murc%253D&md5=ad6760df6b7abc856b68c31980e1da86Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulationsIsralewitz, Barry; Izrailev, Sergei; Schulten, KlausBiophysical Journal (1997), 73 (6), 2972-2979CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)Formation of bacteriorhodopsin (bR) from apoprotein and retinal has been studied exptl., but the actual pathway, including the point of entry, is little understood. Mol. dynamics simulations provide a surprisingly clear prediction. A window between bR helixes E and F in the transmembrane part of the protein can be identified as an entry point for retinal. Steered mol. dynamics, performed by applying a series of external forces in the range of 200-1000 pN over a period of 0.2 ns to retinal, allows one to ext. this chromophore from bR once the Schiff base bond to Lys216 is cleaved. Extn. proceeds until the retinal tail forms a hydrogen bond network with the Ala144, Met145, and Ser183 side groups lining the exit/entry window. The manipulation induces a distortion with a fitted root mean square deviation of coordinates (ignoring retinal, water, and hydrogen atoms) of less than 1.9 Å by the time the retinal carbonyl reaches the protein surface. The forces needed to ext. retinal are due to friction and do not indicate significant potential barriers. The simulations therefore suggest a pathway for the binding of retinal. Water mols. are found to play a crucial role in the binding process.
- 209Jarzynski, C. Nonequilibrium Equality for Free Energy Differences. Phys. Rev. Lett. 1997, 78, 2690, DOI: 10.1103/PhysRevLett.78.2690Google Scholar209https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXisVSrt7c%253D&md5=5e572f64b7e9044fff5af96867602877Nonequilibrium equality for free energy differencesJarzynski, C.Physical Review Letters (1997), 78 (14), 2690-2693CODEN: PRLTAO; ISSN:0031-9007. (American Physical Society)An expression is derived for the equil. free energy difference between two configurations of a system, in terms of an ensemble of finite-time measurements of the work performed in parametrically switching from one configuration to the other. Two well-known identities emerge as limiting cases of this result.
- 210Nelson, M.; Humphrey, W.; Kufrin, R.; Gursoy, A.; Dalke, A.; Kale, L.; Skeel, R.; Schulten, K. MDScope — a Visual Computing Environment for Structural Biology. Comput. Phys. Commun. 1995, 91, 111– 133, DOI: 10.1016/0010-4655(95)00045-HGoogle Scholar210https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXps1Wrtrg%253D&md5=5581371fd83f3a501280347abd691318MDScope - a visual computing environment for structural biologyNelson, Mark; Humphrey, William; Kufrin, Richard; Gursoy, Attila; Dalke, Andrew; Kale, Laxmikant; Skeel, Robert; Schulten, KlausComputer Physics Communications (1995), 91 (1-3), 111-33CODEN: CPHCBZ; ISSN:0010-4655. (Elsevier)MDScope is an integrated set of computational tools which function as an interactive visual computing environment for the simulation and study of biopolymers. This environment consists of three parts: (1) vmd, a mol. visualization program for interactive display of mol. systems; (2) namd, a mol. dynamics program designed for performance, scalability, modularity, and portability, which runs in parallel on a variety of computer platforms; (3) MDComm, a protocol and library which functions as the unifying communication agent between the visualization and simulation components of MDScope. Namd is expressly designed for distributed memory parallel architectures and uses a spatial decompn. parallelization strategy coupled with a multi-threaded, message-driven computation model which reduces inefficiencies due to communication latency. Through the MDComm software, vmd acts as a graphical interface and interactive control for namd, allowing a user running namd to utilize a parallel platform for computational power while visualizing the trajectory as it is computed. Modularity in both vmd and namd is accomplished through an object-oriented design, which facilitates the addn. of features and new algorithms.
- 211Rapaport, D. Interactive Molecular Dynamics. Phys. A 1997, 240, 246– 254, DOI: 10.1016/S0378-4371(97)00148-9Google Scholar211https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXkt1agtLo%253D&md5=8376a0d92a34d61102b994d2dea8e323Interactive molecular dynamicsRapaport, D. C.Physica A: Statistical and Theoretical Physics (Amsterdam) (1997), 240 (1-2), 246-254CODEN: PHYADX; ISSN:0378-4371. (Elsevier)We address the use of visualization and interactivity in mol. dynamics simulation. In an interactive environment the simulator is not only provided with the means to view the system in alternative ways in real-time, but is also able to 'steer' the computation in different directions by changing the governing parameters of the system. The simulational experience can be enhanced significantly by such means. Several examples are outlined.
- 212Rapaport, D. C. An Introduction to Interactive Molecular-Dynamics Simulations. Comput. Phys. 1997, 11, 337– 347, DOI: 10.1063/1.168612Google Scholar212https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmsVCiurs%253D&md5=dd6d05d9bec0be44a4f0deb1ea2828b8An introduction to interactive molecular-dynamics simulationsRapaport, D. C.Computers in Physics (1997), 11 (4), 337-347CODEN: CPHYE2; ISSN:0894-1866. (American Institute of Physics)A review with 8 refs.
- 213Leech, J.; Prins, J. F.; Hermans, J. SMD: Visual Steering of Molecular Dynamics for Protein Design. IEEE Comput. Sci. Eng. 1996, 3, 38– 45, DOI: 10.1109/99.556511Google Scholar213https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXitlSqtQ%253D%253D&md5=6f7100b4048a22f1cdc0a43ab30048b4SMD: visual steering of molecular dynamics for protein designLeech, Jonathan; Prins, Jan F.; Hermans, JanIEEE Computational Science & Engineering (1996), 3 (4), 38-45CODEN: ISCEE4; ISSN:1070-9924. (IEEE Computer Society)SMD, a system for interactively steering mol. dynamics calcns. of protein mols., includes computation, visualization, and communications components. Biochemists can "tug" mols. into different shapes by specifying external forces in the graphical interface, which are added to internal forces representing at. bonds and nonbonded interactions.
- 214Vormoor, O. Quick and Easy Interactive Molecular Dynamics Using Java3D. Comput. Sci. Eng. 2001, 3, 98– 104, DOI: 10.1109/5992.947113Google Scholar214https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFOjt7w%253D&md5=a5b57a2dc0a27f019479fdedba6a44a8Quick and easy interactive molecular dynamics using Java3DVormoor, OliverComputing in Science & Engineering (2001), 3 (5), 98-104CODEN: CSENFA; ISSN:1521-9615. (American Institute of Physics)An interactive mol. dynamics software, called Java Interactive Mol. Dynamics (JIMD), was developed for the study of colloid clusters. JIMD is not a stand-alone interactive mol. dynamic application, but a software package that can be quickly and easily adapted to existing mol. dynamics simulation software. For rendering the mol. system, JIMD uses Java3D, the application programing interface for writing 3D graphics applications in Java.
- 215Stone, J. E.; Gullingsrud, J.; Schulten, K. A System for Interactive Molecular Dynamics Simulation. Proceedings of the 2001 Symposium on Interactive 3D Graphics; ACM: New York, NY, USA, 2001; pp 191– 194.
- 216Grayson, P.; Tajkhorshid, E.; Schulten, K. Mechanisms of Selectivity in Channels and Enzymes Studied with Interactive Molecular Dynamics. Biophys. J. 2003, 85, 36– 48, DOI: 10.1016/S0006-3495(03)74452-X
- 217Férey, N.; Delalande, O.; Grasseau, G.; Baaden, M. A VR Framework for Interacting with Molecular Simulations. Proceedings of the 2008 ACM Symposium on Virtual Reality Software and Technology; ACM: New York, NY, USA, 2008; pp 91– 94.
- 218Dreher, M.; Piuzzi, M.; Turki, A.; Chavent, M.; Baaden, M.; Férey, N.; Limet, S.; Raffin, B.; Robert, S. Interactive Molecular Dynamics: Scaling up to Large Systems. Procedia Comput. Sci. 2013, 18, 20– 29, DOI: 10.1016/j.procs.2013.05.165
- 219Dreher, M.; Prevoteau-Jonquet, J.; Trellet, M.; Piuzzi, M.; Baaden, M.; Raffin, B.; Ferey, N.; Robert, S.; Limet, S. ExaViz: A Flexible Framework to Analyse, Steer and Interact with Molecular Dynamics Simulations. Faraday Discuss. 2014, 169, 119– 142, DOI: 10.1039/C3FD00142C
- 220Stone, J. E.; Kohlmeyer, A.; Vandivort, K. L.; Schulten, K. In Advances in Visual Computing; Bebis, G., Boyle, R., Parvin, B., Koracin, D., Chung, R., Hammound, R., Hussain, M., Kar-Han, T., Crawfis, R., Thalmann, D., Kao, D., Avila, L., Eds.; Lecture Notes in Computer Science; Springer: Berlin, Heidelberg, 2010; Vol. 6454, pp 382– 393.
- 221Luehr, N.; Jin, A. G. B.; Martínez, T. J. Ab Initio Interactive Molecular Dynamics on Graphical Processing Units (GPUs). J. Chem. Theory Comput. 2015, 11, 4536– 4544, DOI: 10.1021/acs.jctc.5b00419Google Scholar221https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVeqtrzP&md5=9d5ff51b17633add948dbacc2c22958fAb Initio Interactive Molecular Dynamics on Graphical Processing Units (GPUs)Luehr, Nathan; Jin, Alex G. B.; Martinez, Todd J.Journal of Chemical Theory and Computation (2015), 11 (10), 4536-4544CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)A virtual mol. modeling kit is developed based on GPU-enabled interactive ab initio mol. dynamics (MD). The code uses the TeraChem and VMD programs with a modified IMD interface. Optimization of the GPU accelerated TeraChem program specifically for small mol. systems is discussed, and a robust multiple time step integrator is employed to accurately integrate strong user-supplied pulling forces. Smooth and responsive visualization techniques are developed to allow interactive manipulation at min. simulation rates below five MD steps per s. Representative calcns. at the Hartree-Fock level of theory are demonstrated for mol. systems contg. up to a few dozen atoms.
- 222Surles, M. C.; Richardson, J. S.; Richardson, D. C.; Brooks, F. P. Sculpting Proteins Interactively: Continual Energy Minimization Embedded in a Graphical Modeling System. Protein Sci. 1994, 3, 198– 210, DOI: 10.1002/pro.5560030205Google Scholar222https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXktlSgt74%253D&md5=2138dd23c7212467e7fe17ab717eaa44Sculpting proteins interactively: continual energy minimization embedded in a graphical modeling systemSurles, Mark C.; Richardson, Jane S.; Richardson, David C.; Brooks, Frederick P., Jr.Protein Science (1994), 3 (), 198-210CODEN: PRCIEI; ISSN:0961-8368.The authors describe a new paradigm for modeling proteins in interactive computer graphics systems - continual maintenance of a phys. valid representation, combined with direct user control and visualization. This is achieved by a fast algorithm for energy minimization, capable of real-time performance an all atoms of a small protein, plus graphically specified user tugs. The modeling system, called Sculpt, rigidly constrains bond strengths, bond angles, and planar groups (similar to existing interactive modeling programs), while it applies elastic restraints to minimize the potential energy due to torsions, hydrogen bonds, and van der Waals and electrostatic interactions (similar to existing batch minimization programs), and user-specific springs. The graphical interface can show bad and(or) favorable contacts, and individual energy terms can be turned on or off to det. their effects and interactions. Sculpt finds a local min. of the total energy that satisfies all the constraints using an augmented Lagrange-multiplier method; calcn. time increases only linearly with the no. of atoms because the matrix of constraint gradients is sparse and banded. On a 100-MHz MIPs R4000 processor (Silicon Graphics Indigo), Sculpt achieves 11 updates per s on a 20-residue fragment and 2 updates per s on an 80-residue protein, using all atoms except non-H-bonding hydrogens, and without electrostatic interactions. Applications of Sculpt are described: to reverse the direction of bundle packing in a designed 4-helix bundle protein, to fold up a 2-stranded β-ribbon into an approx. β-barrel, and to design the sequence and conformation of a 30-residue peptide that mimics one partner of a protein subunit interaction. Computer models that are both interactive and phys. realistic (within the limitations of a given force field) have 2 significant advantages: (1) they make feasible the modeling of very large changes (such as needed for de novo design), and (2) they help the user understand how different energy terms interact to stabilize a given conformation. The Sculpt paradigm combines many of the best features of interactive graphical modeling, energy minimization, and actual phys. models, and the authors propose it as an esp. productive way to use current and future increases in computer speed.
- 223Hanwell, M. D.; Curtis, D. E.; Lonie, D. C.; Vandermeersch, T.; Zurek, E.; Hutchison, G. R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminf. 2012, 4, 17, DOI: 10.1186/1758-2946-4-17Google Scholar223https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVGksLg%253D&md5=f10400f51db314afa780e99403ca748aAvogadro: an advanced semantic chemical editor, visualization, and analysis platformHanwell, Marcus D.; Curtis, Donald E.; Lonie, David C.; Vandermeersch, Tim; Zurek, Eva; Hutchison, Geoffrey R.Journal of Cheminformatics (2012), 4 (), 17CODEN: JCOHB3; ISSN:1758-2946. (Chemistry Central Ltd.)Background: The Avogadro project has developed an advanced mol. editor and visualizer designed for cross-platform use in computational chem., mol. modeling, bioinformatics, materials science, and related areas. It offers flexible, high quality rendering, and a powerful plugin architecture. Typical uses include building mol. structures, formatting input files, and analyzing output of a wide variety of computational chem. packages. By using the CML file format as its native document type, Avogadro seeks to enhance the semantic accessibility of chem. data types. Results: The work presented here details the Avogadro library, which is a framework providing a code library and application programming interface (API) with three-dimensional visualization capabilities; and has direct applications to research and education in the fields of chem., physics, materials science, and biol. The Avogadro application provides a rich graphical interface using dynamically loaded plugins through the library itself. The application and library can each be extended by implementing a plugin module in C++ or Python to explore different visualization techniques, build/manipulate mol. structures, and interact with other programs. We describe some example extensions, one which uses a genetic algorithm to find stable crystal structures, and one which interfaces with the PackMol program to create packed, solvated structures for mol. dynamics simulations. The 1.0 release series of Avogadro is the main focus of the results discussed here. Conclusions: Avogadro offers a semantic chem. builder and platform for visualization and anal. For users, it offers an easy-to-use builder, integrated support for downloading from common databases such as PubChem and the Protein Data Bank, extg. chem. data from a wide variety of formats, including computational chem. output, and native, semantic support for the CML file format. For developers, it can be easily extended via a powerful plugin mechanism to support new features in org. chem., inorg. complexes, drug design, materials, biomols., and simulations.
- 224NANO-D. INRIA, SAMSON Software, Version ∼0.5.0; http://www.samson-connect.net/, 2016 (Accessed: 09 February 2018).Google ScholarThere is no corresponding record for this reference.
- 225Bosson, M.; Richard, C.; Plet, A.; Grudinin, S.; Redon, S. Interactive Quantum Chemistry: A Divide-and-Conquer ASED-MO Method. J. Comput. Chem. 2012, 33, 779– 790, DOI: 10.1002/jcc.22905Google Scholar225https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xkt1Gksw%253D%253D&md5=892979e833f4d542fe8634c28157fd7eInteractive quantum chemistry: A divide-and-conquer ASED-MO methodBosson, Maeel; Richard, Caroline; Plet, Antoine; Grudinin, Sergei; Redon, StephaneJournal of Computational Chemistry (2012), 33 (7), 779-790CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)We present interactive quantum chem. simulation at the atom superposition and electron delocalization MO (ASED-MO) level of theory. Our method is based on the divide-and-conquer (D and C) approach, which we show is accurate and efficient for this non-self-consistent semiempirical theory. The method has a linear complexity in the no. of atoms, scales well with the no. of cores, and has a small prefactor. The time cost is completely controllable, as all steps are performed with direct algorithms, i.e., no iterative schemes are used. We discuss the errors induced by the D and C approach, first empirically on a few examples, and then via a theor. study of two toy models that can be anal. solved for any no. of atoms. Thanks to the precision and speed of the D and C approach, we are able to demonstrate interactive quantum chem. simulations for systems up to a few hundred atoms on a current multicore desktop computer. When drawing and editing mol. systems, interactive simulations provide immediate, intuitive feedback on chem. structures. As the no. of cores on personal computers increases, and larger and larger systems can be dealt with, we believe such interactive simulations-even at lower levels of theory-should thus prove most useful to effectively understand, design and prototype mols., devices and materials. © 2012 Wiley Periodicals, Inc.
- 226Rossi, R.; Isorce, M.; Morin, S.; Flocard, J.; Arumugam, K.; Crouzy, S.; Vivaudou, M.; Redon, S. Adaptive Torsion-Angle Quasi-Statics: A General Simulation Method with Applications to Protein Structure Analysis and Design. Bioinformatics 2007, 23, i408– i417, DOI: 10.1093/bioinformatics/btm191
- 227Bosson, M.; Grudinin, S.; Bouju, X.; Redon, S. Interactive Physically-Based Structural Modeling of Hydrocarbon Systems. J. Comput. Phys. 2012, 231, 2581– 2598, DOI: 10.1016/j.jcp.2011.12.006Google Scholar227https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1Ogsbw%253D&md5=597f128c081cf549f0ef8667d746861cInteractive physically-based structural modeling of hydrocarbon systemsBosson, Mael; Grudinin, Sergei; Bouju, Xavier; Redon, StephaneJournal of Computational Physics (2012), 231 (6), 2581-2598CODEN: JCTPAH; ISSN:0021-9991. (Elsevier Inc.)Hydrocarbon systems have been intensively studied via numerical methods, including electronic structure computations, mol. dynamics and Monte Carlo simulations. Typically, these methods require an initial structural model (at. positions and types, topol., etc.) that may be produced using scripts and/or modeling tools. For many systems, however, these building methods may be ineffective, as the user may have to specify the positions of numerous atoms while maintaining structural plausibility. In this paper, we present an interactive phys.-based modeling tool to construct structural models of hydrocarbon systems. As the user edits the geometry of the system, at. positions are also influenced by the Brenner potential, a well-known bond-order reactive potential. In order to be able to interactively edit systems contg. numerous atoms, we introduce a new adaptive simulation algorithm, as well as a novel algorithm to incrementally update the forces and the total potential energy based on the list of updated relative at. positions. The computational cost of the adaptive simulation algorithm depends on user-defined error thresholds, and our potential update algorithm depends linearly with the no. of updated bonds. This allows us to enable efficient phys.-based editing, since the computational cost is decoupled from the no. of atoms in the system. We show that our approach may be used to effectively build realistic models of hydrocarbon structures that would be difficult or impossible to produce using other tools.
- 228Bosson, M.; Grudinin, S.; Redon, S. Block-Adaptive Quantum Mechanics: An Adaptive Divide-and-Conquer Approach to Interactive Quantum Chemistry. J. Comput. Chem. 2013, 34, 492– 504, DOI: 10.1002/jcc.23157
- 229Jaillet, L.; Artemova, S.; Redon, S. IM-UFF: Extending the Universal Force Field for Interactive Molecular Modeling. J. Mol. Graphics Modell. 2017, 77, 350– 362, DOI: 10.1016/j.jmgm.2017.08.023Google Scholar229https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFGht7zL&md5=d8a6e882b109aa01ac2ce81758ec234bIM-UFF: Extending the universal force field for interactive molecular modelingJaillet, Leonard; Artemova, Svetlana; Redon, StephaneJournal of Molecular Graphics & Modelling (2017), 77 (), 350-362CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)The universal force field (UFF) is a broadly applicable classical force field that contains parameters for almost every atom type of the periodic table. This force field is non-reactive, i.e. the topol. of the system under study is considered as fixed and no creation or breaking of covalent bonds is possible. This paper introduces interactive modeling-UFF (IM-UFF), an extension of UFF that combines the possibility to significantly modify mol. structures (as with reactive force fields) with a broad diversity of supported systems thanks to the universality of UFF. Such an extension lets the user easily build and edit mol. systems interactively while being guided by physics based inter-at. forces. This approach introduces weighted atom types and weighted bonds, used to update topologies and atom parameterizations at every time step of a simulation. IM-UFF has been evaluated on a large set of benchmarks and is proposed as a self-contained implementation integrated in a new module for the SAMSON software platform for computational nanoscience available at http://www.samson-connect.net.
- 230Disz, T.; Papka, M.; Stevens, R.; Pellegrino, M.; Taylor, V. Virtual Reality Visualization of Parallel Molecular Dynamics Simulation. Proceedings of High-Performance Computing 1995, 483– 487Google ScholarThere is no corresponding record for this reference.
- 231Akkiraju, N.; Edelsbrunner, H.; Fu, P.; Qian, J. Viewing Geometric Protein Structures from inside a CAVE. IEEE Comput. Graph. Appl. 1996, 16, 58– 61, DOI: 10.1109/38.511855
- 232Salvadori, A.; Del Frate, G.; Pagliai, M.; Mancini, G.; Barone, V. Immersive Virtual Reality in Computational Chemistry: Applications to the Analysis of QM and MM Data. Int. J. Quantum Chem. 2016, 116, 1731– 1746, DOI: 10.1002/qua.25207Google Scholar232https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFCrurnF&md5=bbfba250da95eba7fbd0583621fcb11dImmersive virtual reality in computational chemistry: Applications to the analysis of QM and MM dataSalvadori, Andrea; Del Frate, Gianluca; Pagliai, Marco; Mancini, Giordano; Barone, VincenzoInternational Journal of Quantum Chemistry (2016), 116 (22), 1731-1746CODEN: IJQCB2; ISSN:0020-7608. (John Wiley & Sons, Inc.)The role of Virtual Reality (VR) tools in mol. sciences is analyzed in this contribution through the presentation of the Caffeine software to the quantum chem. community. Caffeine, developed at Scuola Normale Superiore, is specifically tailored for mol. representation and data visualization with VR systems, such as VR theaters and helmets. Usefulness and advantages that can be gained by exploiting VR are here reported, considering few examples specifically selected to illustrate different level of theory and mol. representation.
- 233García-Hernández, R. J.; Kranzlmüller, D. Virtual Reality Toolset for Material Science: NOMAD VR Tools. Augmented Reality, Virtual Reality, and Computer Graphics . 2017; pp 309– 319.
- 234Haase, H.; Strassner, J.; Dai, F. VR Techniques for the Investigation of Molecule Data. Computers & Graphics 1996, 20, 207– 217, DOI: 10.1016/0097-8493(95)00127-1
- 235Sauer, C.; Hastings, W.; Okamura, A. M. Virtual Environment for Exploring Atomic Bonding. Proceedings of EuroHaptics 2004; International Design Foundation, 2004; pp 232– 239.Google ScholarThere is no corresponding record for this reference.
- 236Norrby, M.; Grebner, C.; Eriksson, J.; Boström, J. Molecular Rift: Virtual Reality for Drug Designers. J. Chem. Inf. Model. 2015, 55, 2475– 2484, DOI: 10.1021/acs.jcim.5b00544Google Scholar236https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslGjurrL&md5=9a206f1ec098ca25df4a6b81f217891fMolecular Rift: Virtual Reality for Drug DesignersNorrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Bostroem, JonasJournal of Chemical Information and Modeling (2015), 55 (11), 2475-2484CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate phys. presence in the real world-a virtual reality. This is relevant to drug discovery since mol. models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Mol. Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for std. input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Mol. Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chem. and education. Mol. Rift is open source and can be downloaded from GitHub.
- 237Harvey, E.; Gingold, C. Haptic Representation of the Atom. 2000 IEEE Conference on Information Visualization. An International Conference on Computer Visualization and Graphics; IEEE, 2000; pp 232– 235.
- 238Comai, S.; Mazza, D. A Haptic-Enhanced System for Molecular Sensing. Human-Computer Interaction – INTERACT 2009; Springer, 2009; pp 493– 496.
- 239Satoh, H.; Nukada, T.; Akahane, K.; Sato, M. Construction of Basic Haptic Systems for Feeling the Intermolecular Force in Molecular Models. J. Comput. Aided Chem. 2006, 7, 38– 47, DOI: 10.2751/jcac.7.38
- 240Stocks, M. B.; Hayward, S.; Laycock, S. D. Interacting with the Biomolecular Solvent Accessible Surface via a Haptic Feedback Device. BMC Struct. Biol. 2009, 9, 69, DOI: 10.1186/1472-6807-9-69Google Scholar240https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjkvVegtw%253D%253D&md5=863ad1d411a653bccac4b93267584afbInteracting with the biomolecular solvent accessible surface via a haptic feedback deviceStocks Matthew B; Hayward Steven; Laycock Stephen DBMC structural biology (2009), 9 (), 69 ISSN:.BACKGROUND: From the 1950s computer based renderings of molecules have been produced to aid researchers in their understanding of biomolecular structure and function. A major consideration for any molecular graphics software is the ability to visualise the three dimensional structure of the molecule. Traditionally, this was accomplished via stereoscopic pairs of images and later realised with three dimensional display technologies. Using a haptic feedback device in combination with molecular graphics has the potential to enhance three dimensional visualisation. Although haptic feedback devices have been used to feel the interaction forces during molecular docking they have not been used explicitly as an aid to visualisation. RESULTS: A haptic rendering application for biomolecular visualisation has been developed that allows the user to gain three-dimensional awareness of the shape of a biomolecule. By using a water molecule as the probe, modelled as an oxygen atom having hard-sphere interactions with the biomolecule, the process of exploration has the further benefit of being able to determine regions on the molecular surface that are accessible to the solvent. This gives insight into how awkward it is for a water molecule to gain access to or escape from channels and cavities, indicating possible entropic bottlenecks. In the case of liver alcohol dehydrogenase bound to the inhibitor SAD, it was found that there is a channel just wide enough for a single water molecule to pass through. Placing the probe coincident with crystallographic water molecules suggests that they are sometimes located within small pockets that provide a sterically stable environment irrespective of hydrogen bonding considerations. CONCLUSION: By using the software, named HaptiMol ISAS (available from http://www.haptimol.co.uk), one can explore the accessible surface of biomolecules using a three-dimensional input device to gain insights into the shape and water accessibility of the biomolecular surface that cannot be so easily attained using conventional molecular graphics software.
- 241Sankaranarayanan, G.; Weghorst, S.; Sanner, M.; Gillet, A.; Olson, A. Role of Haptics in Teaching Structural Molecular Biology. 11th Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems; IEEE, 2003; pp 363– 366.
- 242Persson, P. B.; Cooper, M. D.; Tibell, L. A. E.; Ainsworth, S.; Ynnerman, A.; Jonsson, B. H. Designing and Evaluating a Haptic System for Biomolecular Education. 2007 IEEE Virtual Reality Conference; IEEE, 2007; pp 171– 178.
- 243Sourina, O.; Torres, J.; Wang, J. In Transactions on Edutainment II; Pan, Z., Cheok, A. D., Müller, W., Rhalibi, A. E., Eds.; Springer: Berlin, Heidelberg, 2009; Chapter Visual Haptic-Based Biomolecular Docking and Its Applications in E-Learning, pp 105– 118.
- 244Bivall, P.; Ainsworth, S.; Tibell, L. A. E. Do Haptic Representations Help Complex Molecular Learning?. Sci. Educ. 2011, 95, 700– 719, DOI: 10.1002/sce.20439
- 245Chastine, J. W.; Zhu, Y.; Brooks, J. C.; Owen, G. S.; Harrison, R. W.; Weber, I. T. A Collaborative Multi-View Virtual Environment for Molecular Visualization and Modeling. Coordinated and Multiple Views in Exploratory Visualization; IEEE, 2005; pp 77– 84.
- 246Nadan, T.; Haffegee, A.; Watson, K. Collaborative and Parallelized Immersive Molecular Docking. International Conference on Computational Science 2009, 5545, 737– 745, DOI: 10.1007/978-3-642-01973-9_82
- 247Hou, X.; Sourina, O.; Klimenko, S. Visual Haptic-Based Collaborative Molecular Docking. IFMBE Proceedings 2014, 43, 360– 363, DOI: 10.1007/978-3-319-02913-9_92
- 248Davies, E.; Tew, P.; Glowacki, D.; Smith, J.; Mitchell, T. Evolutionary and Biologically Inspired Music, Sound, Art and Design. Proceedings of the 5th International Conference, EvoMUSART 2016, Porto, Portugal, March 30 – April 1, 2016; Johnson, C., Ciesielski, V., Correia, J. a., Machado, P., Eds.; Springer International Publishing, 2016; pp 17– 30.Google ScholarThere is no corresponding record for this reference.
- 249Mitchell, T.; Hyde, J.; Tew, P.; Glowacki, D. R. Danceroom Spectroscopy: At the Frontiers of Physics, Performance, Interactive Art and Technology. Leonardo 2016, 49, 138– 147, DOI: 10.1162/LEON_a_00924
- 250Marti, K. H.; Reiher, M. Haptic Quantum Chemistry. J. Comput. Chem. 2009, 30, 2010– 2020, DOI: 10.1002/jcc.21201Google Scholar250https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXptleqsLw%253D&md5=a0b7305f8d60a1b2a5c8bf5938d6f2a5Haptic quantum chemistryMarti, Konrad H.; Reiher, MarkusJournal of Computational Chemistry (2009), 30 (13), 2010-2020CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)We present an implementation designed to phys. experience quantum mech. forces between reactants in chem. reactions. This allows one to screen the profile of potential energy surfaces for the study of reaction mechanisms. For this, we have developed a interface between the user and a virtual lab. by means of a force-feedback haptic device. Potential energy surfaces of chem. reactions can be explored efficiently by rendering in the haptic device the gradients calcd. with first-principles methods. The underlying potential energy surface is accurately fitted on the fly by the interpolating moving least-squares (IMLS) scheme to a grid of quantum chem. electronic energies (and geometric gradients). In addn., we introduce a new IMLS-based method to locate min.-energy paths between two points on a potential energy surface. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009.
- 251Haag, M. P.; Marti, K. H.; Reiher, M. Generation of Potential Energy Surfaces in High Dimensions and Their Haptic Exploration. ChemPhysChem 2011, 12, 3204– 3213, DOI: 10.1002/cphc.201100539Google Scholar251https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFKrtLjL&md5=df3aa356658e41578110e6b4dd5228aaGeneration of Potential Energy Surfaces in High Dimensions and Their Haptic ExplorationHaag, Moritz P.; Marti, Konrad H.; Reiher, MarkusChemPhysChem (2011), 12 (17), 3204-3213CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)A method is proposed for the automated generation of potential energy surfaces in high dimensions. It combines the existing algorithm for the definition of new energy data points, based on the interpolating moving least-squares algorithm with a simulated annealing procedure. This method is then studied in a haptic quantum chem. environment that requires a fast evaluation of gradients on a potential energy surface with automatic improvement of its accuracy. As an example we investigate the nitrogen binding pathway in the Schrock dinitrogen fixation complex with this set-up.
- 252Haag, M. P.; Reiher, M. Real-Time Quantum Chemistry. Int. J. Quantum Chem. 2013, 113, 8– 20, DOI: 10.1002/qua.24336Google Scholar252https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVykt7fP&md5=ec7746303ee168218745cb0b4539fdb9Real-time quantum chemistryHaag, Moritz P.; Reiher, MarkusInternational Journal of Quantum Chemistry (2013), 113 (1), 8-20CODEN: IJQCB2; ISSN:0020-7608. (John Wiley & Sons, Inc.)Significant progress in the development of efficient and fast algorithms for quantum chem. calcns. has been made in the past two decades. The main focus has always been the desire to be able to treat ever larger mols. or mol. assemblies-esp. linear and sublinear scaling techniques are devoted to the accomplishment of this goal. However, as many chem. reactions are rather local, they usually involve only a limited no. of atoms so that models of about 200 (or even less) atoms embedded in a suitable environment are sufficient to study their mechanisms. Thus, the system size does not need to be enlarged, but remains const. for reactions of this type that can be described by less than 200 atoms. The question then arises how fast one can obtain the quantum chem. results. This question is not directly answered by linear-scaling techniques. In fact, ideas such as haptic quantum chem. (HQC) or interactive quantum chem. require an immediate provision of quantum chem. information which demands the calcn. of data in "real time." In this perspective, we aim at a definition of real-time quantum chem., explore its realm and eventually discuss applications in the field of HQC. For the latter, we elaborate whether a direct approach is possible by virtue of real-time quantum chem. © 2012 Wiley Periodicals, Inc.
- 253Haag, M. P.; Reiher, M. Studying Chemical Reactivity in a Virtual Environment. Faraday Discuss. 2014, 169, 89– 118, DOI: 10.1039/C4FD00021HGoogle Scholar253https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7nF&md5=8b0b85c38bb608e1d9b8b6fa79ef8760Studying chemical reactivity in a virtual environmentHaag, Moritz P.; Reiher, MarkusFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 89-118CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Chem. reactivity of a set of reactants is detd. by its potential (electronic) energy (hyper)surface. The high dimensionality of this surface renders it difficult to efficiently explore reactivity in a large reactive system. Exhaustive sampling techniques and search algorithms are not straightforward to employ as it is not clear which explored path will eventually produce the min. energy path of a reaction passing through a transition structure. Here, the chemist's intuition would be of invaluable help, but it cannot be easily exploited because (1) no intuitive and direct tool for the scientist to manipulate mol. structures is currently available and because (2) quantum chem. calcns. are inherently expensive in terms of computational effort. In this work, we elaborate on how the chemist can be reintroduced into the exploratory process within a virtual environment that provides immediate feedback and intuitive tools to manipulate a reactive system. We work out in detail how this immersion should take place. We provide an anal. of modern semi-empirical methods which already today are candidates for the interactive study of chem. reactivity. Implications of manual structure manipulations for their phys. meaning and chem. relevance are carefully analyzed in order to provide sound theor. foundations for the interpretation of the interactive reactivity exploration.
- 254Haag, M. P.; Vaucher, A. C.; Bosson, M.; Redon, S.; Reiher, M. Interactive Chemical Reactivity Exploration. ChemPhysChem 2014, 15, 3301– 3319, DOI: 10.1002/cphc.201402342Google Scholar254https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFSgsrnM&md5=5c26a58bb25aa70f7a71ebf0c93ea3ccInteractive Chemical Reactivity ExplorationHaag, Moritz P.; Vaucher, Alain C.; Bosson, Mael; Redon, Stephane; Reiher, MarkusChemPhysChem (2014), 15 (15), 3301-3319CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)Elucidating chem. reactivity in complex mol. assemblies of a few hundred atoms is, despite the remarkable progress in quantum chem., still a major challenge. Black-box search methods to find intermediates and transition-state structures might fail in such situations because of the high-dimensionality of the potential energy surface. Here, we propose the concept of interactive chem. reactivity exploration to effectively introduce the chemist's intuition into the search process. We employ a haptic pointer device with force feedback to allow the operator the direct manipulation of structures in three dimensions along with simultaneous perception of the quantum mech. response upon structure modification as forces. We elaborate on the details of how such an interactive exploration should proceed and which tech. difficulties need to be overcome. All reactivity-exploration concepts developed for this purpose have been implemented in the SAMSON programming environment.
- 255Mühlbach, A. H.; Vaucher, A. C.; Reiher, M. Accelerating Wave Function Convergence in Interactive Quantum Chemical Reactivity Studies. J. Chem. Theory Comput. 2016, 12, 1228– 1235, DOI: 10.1021/acs.jctc.5b01156
- 256Atsumi, T.; Nakai, H. Molecular Orbital Propagation to Accelerate Self-Consistent-Field Convergence in an Ab Initio Molecular Dynamics Simulation. J. Chem. Phys. 2008, 128, 094101, DOI: 10.1063/1.2839857Google Scholar256https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXjtl2qt74%253D&md5=1b02d7ccbc0390afd6bc6421fe3d2f36Molecular orbital propagation to accelerate self-consistent-field convergence in an ab initio molecular dynamics simulationAtsumi, Teruo; Nakai, HiromiJournal of Chemical Physics (2008), 128 (9), 094101/1-094101/9CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Based on the idea of MO propagation, we propose a novel effective method for predicting initial guesses for the self-consistent-field calcns. in direct ab initio mol. dynamics (AIMD) simulations. This method, called LIMO, adopts the Lagrange interpolation (LI) polynomial technique and predicts initial MO coeffs. at the next AIMD step by using several previous results. Taking into account the crossing and/or mixing of MOs leads to orbital invariant formulas for the LIMO method. We also propose a simple method for detg. the optimal degree of the LI polynomial, which corresponds to the no. of previous steps. Numerical tests confirm that this proposed method is both effective and feasible. (c) 2008 American Institute of Physics.
- 257Atsumi, T.; Nakai, H. Acceleration of Self-Consistent-Field Convergence in Ab Initio Molecular Dynamics and Monte Carlo Simulations and Geometry Optimization. Chem. Phys. Lett. 2010, 490, 102– 108, DOI: 10.1016/j.cplett.2010.03.012Google Scholar257https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkt1ygt74%253D&md5=378feecb4e22a46ab096a8c43c0e5a9eAcceleration of self-consistent-field convergence in ab initio molecular dynamics and Monte Carlo simulations and geometry optimizationAtsumi, Teruo; Nakai, HiromiChemical Physics Letters (2010), 490 (1-3), 102-108CODEN: CHPLBC; ISSN:0009-2614. (Elsevier B.V.)We propose a novel acceleration method for self-consistent-field calcns. in direct ab initio mol. dynamics/Monte Carlo (AIMD/AIMC) simulations and geometry optimization. This acceleration method, so-called LSMO, predicts an initial guess of MOs (MOs) for the next simulation step by using the geometric information with the least-squares technique. Numerical tests confirm that the LSMO method is both effective and feasible in the AIMD/AIMC simulations and geometry optimization.
- 258Vaucher, A. C.; Haag, M. P.; Reiher, M. Real-Time Feedback from Iterative Electronic Structure Calculations. J. Comput. Chem. 2016, 37, 805– 812, DOI: 10.1002/jcc.24268Google Scholar258https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVCltLrK&md5=847dceab1dfd98f653c508db8961b9adReal-time feedback from iterative electronic structure calculationsVaucher, Alain C.; Haag, Moritz P.; Reiher, MarkusJournal of Computational Chemistry (2016), 37 (9), 805-812CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Real-time feedback from iterative electronic structure calcns. requires to mediate between the inherently unpredictable execution times of the iterative algorithm used and the necessity to provide data in fixed and short time intervals for real-time rendering. We introduce the concept of a mediator as a component able to deal with infrequent and unpredictable ref. data to generate reliable feedback. In the context of real-time quantum chem., the mediator takes the form of a surrogate potential that has the same local shape as the first-principles potential and can be evaluated efficiently to deliver at. forces as real-time feedback. The surrogate potential is updated continuously by electronic structure calcns. and guarantees to provide a reliable response to the operator for any mol. structure. To demonstrate the application of iterative electronic structure methods in real-time reactivity exploration, we implement self-consistent semiempirical methods as the data source and apply the surrogate-potential mediator to deliver reliable real-time feedback. © 2015 Wiley Periodicals, Inc.
- 259Vaucher, A. C.; Reiher, M. Steering Orbital Optimization out of Local Minima and Saddle Points Toward Lower Energy. J. Chem. Theory Comput. 2017, 13, 1219– 1228, DOI: 10.1021/acs.jctc.7b00011Google Scholar259https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivVKqs78%253D&md5=94b5a248bcc23b8c0d0e71e82c8be2f1Steering Orbital Optimization out of Local Minima and Saddle Points Toward Lower EnergyVaucher, Alain C.; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (3), 1219-1228CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The general procedure underlying Hartree-Fock and Kohn-Sham d. functional theory calcns. consists in optimizing orbitals for a self-consistent soln. of the Roothaan-Hall equations in an iterative process. It is often ignored that multiple self-consistent solns. can exist, several of which may correspond to min. of the energy functional. In addn. to the difficulty sometimes encountered to converge the calcn. to a self-consistent soln., one must ensure that the correct self-consistent soln. was found, typically the one with the lowest electronic energy. Convergence to an unwanted soln. is in general not trivial to detect and will deliver incorrect energy and mol. properties and accordingly a misleading description of chem. reactivity. Wrong conclusions based on incorrect SCF convergence are particularly cumbersome in automated calcns. met in high-throughput virtual screening, structure optimizations, ab initio mol. dynamics, and in real-time explorations of chem. reactivity, where the vast amt. of data can hardly be manually inspected. Here, we introduce a fast and automated approach to detect and cure incorrect orbital convergence, which is esp. suited for electronic structure calcns. on sequences of mol. structures. Our approach consists of a randomized perturbation of the converged electron d. (matrix) intended to push orbital convergence to solns. that correspond to another stationary point (of potentially lower electronic energy) in the variational parameter space of an electronic wave function approxn.
- 260Vaucher, A. C.; Reiher, M. Molecular Propensity as a Driver for Explorative Reactivity Studies. J. Chem. Inf. Model. 2016, 56, 1470– 1478, DOI: 10.1021/acs.jcim.6b00264Google Scholar260https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xht1WntbrN&md5=ba5071e8f71e85291382737cf389899aMolecular Propensity as a Driver for Explorative Reactivity StudiesVaucher, Alain C.; Reiher, MarkusJournal of Chemical Information and Modeling (2016), 56 (8), 1470-1478CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Quantum chem. studies of reactivity involve calcns. on a large no. of mol. structures and the comparison of their energies. Already the setup of these calcns. limits the scope of the results that one will obtain, because several system-specific variables such as the charge and spin need to be set prior to the calcn. For a reliable exploration of reaction mechanisms, a considerable no. of calcns. with varying global parameters must be taken into account, or important facts about the reactivity of the system under consideration can remain undetected. For example, one could miss crossings of potential energy surfaces for different spin states or might not note that a mol. is prone to oxidn. Here, we introduce the concept of mol. propensity to account for the predisposition of a mol. system to react across different electronic states in certain nuclear configurations or with other reactants present in the reaction liquor. Within our real-time quantum chem. framework, we developed an algorithm that automatically detects and flags such a propensity of a system under consideration.
- 261Heuer, M. A.; Vaucher, A. C.; Haag, M. P.; Reiher, M. Integrated Reaction Path Processing from Sampled Structure Sequences. J. Chem. Theory Comput. 2018, 14, 2052– 2062, DOI: 10.1021/acs.jctc.8b00019Google Scholar261https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXktFWgs78%253D&md5=aa7c203a39a0cc9c876174b2c517e4c5Integrated Reaction Path Processing from Sampled Structure SequencesHeuer, Michael A.; Vaucher, Alain C.; Haag, Moritz P.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (4), 2052-2062CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Sampled structure sequences obtained, for instance, from real-time reactivity explorations or first-principles mol. dynamics simulations contain valuable information about chem. reactivity. Eventually, such sequences allow for the construction of reaction networks that are required for the kinetic anal. of chem. systems. For this purpose, however, the sampled information must be processed to obtain stable chem. structures and assocd. transition states. The manual extn. of valuable information from such reaction paths is straightforward but unfeasible for large and complex reaction networks. For real-time quantum chem., this implies automatization of the extn. and relaxation process while maintaining immersion in the virtual chem. environment. Here, we describe an efficient path processing scheme for the on-the-fly construction of an exploration network by approximating the explored paths as continuous basis-spline curves.
- 262Reiher, M.; SCINE – Software for Chemical Interaction Networks. http://scine.ethz.ch (Accessed: 12. September 2018).Google ScholarThere is no corresponding record for this reference.
Cited By
Click to copy section linkSection link copied!
This article is cited by 162 publications.
- Ammar Mahmood, Frank Dehn, Peter Thissen. Carbonation under Varying Humidity Conditions: A 3D Micro-Scale Kinetic Monte Carlo Approach. Langmuir 2025, Article ASAP.EI检索SCI升级版 化学2区SCI基础版 化学3区IF 3.7SWJTU A++
- Jan A. Meissner, Jan Meisner. Acceleration of Diffusion in Ab Initio Nanoreactor Molecular Dynamics and Application to Hydrogen Sulfide Oxidation. Journal of Chemical Theory and Computation 2025, 21 (1) , 218-229. https://doi.org/10.1021/acs.jctc.4c00826SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Charlotte H. Müller, Miguel Steiner, Jan P. Unsleber, Thomas Weymuth, Moritz Bensberg, Katja-Sophia Csizi, Maximilian Mörchen, Paul L. Türtscher, Markus Reiher. Heron: Visualizing and Controlling Chemical Reaction Explorations and Networks. The Journal of Physical Chemistry A 2024, 128 (41) , 9028-9044. https://doi.org/10.1021/acs.jpca.4c03936EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Miko M. Stulajter, Dmitrij Rappoport. Reaction Networks Resemble Low-Dimensional Regular Lattices. Journal of Chemical Theory and Computation 2024, 20 (18) , 8035-8048. https://doi.org/10.1021/acs.jctc.4c00810SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Karthik Srinivasan, Anjana Puliyanda, Vinay Prasad. Identification of Reaction Network Hypotheses for Complex Feedstocks from Spectroscopic Measurements with Minimal Human Intervention. The Journal of Physical Chemistry A 2024, 128 (23) , 4714-4729. https://doi.org/10.1021/acs.jpca.4c01592EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Moritz Bensberg, Markus Reiher. Uncertainty-Aware First-Principles Exploration of Chemical Reaction Networks. The Journal of Physical Chemistry A 2024, 128 (22) , 4532-4547. https://doi.org/10.1021/acs.jpca.3c08386EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Yuheng Ding, Bo Qiang, Qixuan Chen, Yiqiao Liu, Liangren Zhang, Zhenming Liu. Exploring Chemical Reaction Space with Machine Learning Models: Representation and Feature Perspective. Journal of Chemical Information and Modeling 2024, 64 (8) , 2955-2970. https://doi.org/10.1021/acs.jcim.4c00004EI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Yu Harabuchi, Tomohiko Yokoyama, Wataru Matsuoka, Taihei Oki, Satoru Iwata, Satoshi Maeda. Differentiating the Yield of Chemical Reactions Using Parameters in First-Order Kinetic Equations to Identify Elementary Steps That Control the Reactivity from Complicated Reaction Path Networks. The Journal of Physical Chemistry A 2024, 128 (14) , 2883-2890. https://doi.org/10.1021/acs.jpca.4c00204EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Yutai Zhang, Chao Xu, Zhenggang Lan. Automated Exploration of Reaction Networks and Mechanisms Based on Metadynamics Nanoreactor Simulations. Journal of Chemical Theory and Computation 2023, 19 (23) , 8718-8731. https://doi.org/10.1021/acs.jctc.3c00752SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Taisuke Hasegawa, Satoshi Hagiwara, Minoru Otani, Satoshi Maeda. A Combined Reaction Path Search and Hybrid Solvation Method for the Systematic Exploration of Elementary Reactions at the Solid–Liquid Interface. The Journal of Physical Chemistry Letters 2023, 14 (39) , 8796-8804. https://doi.org/10.1021/acs.jpclett.3c02233EI检索SCI升级版 化学2区SCI基础版 化学2区IF 4.8SWJTU A++
- Jan P. Unsleber. Accelerating Reaction Network Explorations with Automated Reaction Template Extraction and Application. Journal of Chemical Information and Modeling 2023, 63 (11) , 3392-3403. https://doi.org/10.1021/acs.jcim.3c00102EI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Wataru Matsuoka, Yu Harabuchi, Satoshi Maeda. Virtual Ligand Strategy in Transition Metal Catalysis Toward Highly Efficient Elucidation of Reaction Mechanisms and Computational Catalyst Design. ACS Catalysis 2023, 13 (8) , 5697-5711. https://doi.org/10.1021/acscatal.3c00576EI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.3
- Atsuyuki Nakao, Yu Harabuchi, Satoshi Maeda, Koji Tsuda. Exploring the Quantum Chemical Energy Landscape with GNN-Guided Artificial Force. Journal of Chemical Theory and Computation 2023, 19 (3) , 713-717. https://doi.org/10.1021/acs.jctc.2c01061SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Judit Zádor, Carles Martí, Ruben Van de Vijver, Sommer L. Johansen, Yoona Yang, Hope A. Michelsen, Habib N. Najm. Automated Reaction Kinetics of Gas-Phase Organic Species over Multiwell Potential Energy Surfaces. The Journal of Physical Chemistry A 2023, 127 (3) , 565-588. https://doi.org/10.1021/acs.jpca.2c06558EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Bastian Bjerkem Skjelstad, Yuh Hijikata, Satoshi Maeda. Early-Stage Formation of the SIFSIX-3-Zn Metal–Organic Framework: An Automated Computational Study. Inorganic Chemistry 2023, 62 (3) , 1210-1217. https://doi.org/10.1021/acs.inorgchem.2c03681EI检索SCI升级版 化学2区SCI基础版 化学2区IF 4.3SWJTU A++
- Paul L. Türtscher, Markus Reiher. Pathfinder─Navigating and Analyzing Chemical Reaction Networks with an Efficient Graph-Based Approach. Journal of Chemical Information and Modeling 2023, 63 (1) , 147-160. https://doi.org/10.1021/acs.jcim.2c01136EI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Tsuyoshi Mita, Hideaki Takano, Hiroki Hayashi, Wataru Kanna, Yu Harabuchi, K. N. Houk, Satoshi Maeda. Prediction of High-Yielding Single-Step or Cascade Pericyclic Reactions for the Synthesis of Complex Synthetic Targets. Journal of the American Chemical Society 2022, 144 (50) , 22985-23000. https://doi.org/10.1021/jacs.2c09830EI检索SCI升级版 化学1区SCI基础版 化学1区IF 14.4SWJTU A++
- Stefan Gugler, Markus Reiher. Quantum Chemical Roots of Machine-Learning Molecular Similarity Descriptors. Journal of Chemical Theory and Computation 2022, 18 (11) , 6670-6689. https://doi.org/10.1021/acs.jctc.2c00718SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Alexandra Stan, Beatriz von der Esch, Christian Ochsenfeld. Fully Automated Generation of Prebiotically Relevant Reaction Networks from Optimized Nanoreactor Simulations. Journal of Chemical Theory and Computation 2022, 18 (11) , 6700-6712. https://doi.org/10.1021/acs.jctc.2c00754SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Umberto Raucci, David M. Sanchez, Todd J. Martínez, Michele Parrinello. Enhanced Sampling Aided Design of Molecular Photoswitches. Journal of the American Chemical Society 2022, 144 (42) , 19265-19271. https://doi.org/10.1021/jacs.2c04419EI检索SCI升级版 化学1区SCI基础版 化学1区IF 14.4SWJTU A++
- Idil Ismail, Raphael Chantreau Majerus, Scott Habershon. Graph-Driven Reaction Discovery: Progress, Challenges, and Future Opportunities. The Journal of Physical Chemistry A 2022, 126 (40) , 7051-7069. https://doi.org/10.1021/acs.jpca.2c06408EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Philipp Pracht, Christoph Bannwarth. Fast Screening of Minimum Energy Crossing Points with Semiempirical Tight-Binding Methods. Journal of Chemical Theory and Computation 2022, 18 (10) , 6370-6385. https://doi.org/10.1021/acs.jctc.2c00578SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Bastian Bjerkem Skjelstad, Trygve Helgaker, Satoshi Maeda, David Balcells. Oxyl Character and Methane Hydroxylation Mechanism in Heterometallic M(O)Co3O4 Cubanes (M = Cr, Mn, Fe, Mo, Tc, Ru, and Rh). ACS Catalysis 2022, 12 (19) , 12326-12335. https://doi.org/10.1021/acscatal.2c03748EI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.3
- Jan P. Unsleber, Stephanie A. Grimmel, Markus Reiher. Chemoton 2.0: Autonomous Exploration of Chemical Reaction Networks. Journal of Chemical Theory and Computation 2022, 18 (9) , 5393-5409. https://doi.org/10.1021/acs.jctc.2c00193SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Qinxuan Wang, Jiun-Le Shih, Ka Yi Tsui, Croix J. Laconsay, Dean J. Tantillo, Jeremy A. May. Experimental and Computational Mechanistic Study of Carbonazidate-Initiated Cascade Reactions. The Journal of Organic Chemistry 2022, 87 (14) , 8983-9000. https://doi.org/10.1021/acs.joc.2c00696EI检索SCI升级版 化学2区SCI基础版 化学2区IF 3.3
- Diego Garay-Ruiz, Moises Álvarez-Moreno, Carles Bo, Emilio Martínez-Núñez. New Tools for Taming Complex Reaction Networks: The Unimolecular Decomposition of Indole Revisited. ACS Physical Chemistry Au 2022, 2 (3) , 225-236. https://doi.org/10.1021/acsphyschemau.1c00051IF 3.7
- Lin Ji, Yue Li, Jie Wang, An Ning, Naixin Zhang, Shengyao Liang, Jiyun He, Tianyu Zhang, Zexing Qu, Jiali Gao. Community Reaction Network Reduction for Constructing a Coarse-Grained Representation of Combustion Reaction Mechanisms. Journal of Chemical Information and Modeling 2022, 62 (10) , 2352-2364. https://doi.org/10.1021/acs.jcim.2c00240EI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Yosuke Sumiya, Yu Harabuchi, Yuuya Nagata, Satoshi Maeda. Quantum Chemical Calculations to Trace Back Reaction Paths for the Prediction of Reactants. JACS Au 2022, 2 (5) , 1181-1188. https://doi.org/10.1021/jacsau.2c00157IF 8.5
- Xin Chen, Meiyi Liu, Jiali Gao. CARNOT: a Fragment-Based Direct Molecular Dynamics and Virtual–Reality Simulation Package for Reactive Systems. Journal of Chemical Theory and Computation 2022, 18 (3) , 1297-1313. https://doi.org/10.1021/acs.jctc.1c01032SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Lukas Krep, Indu Sekhar Roy, Wassja Kopp, Felix Schmalz, Can Huang, Kai Leonhard. Efficient Reaction Space Exploration with ChemTraYzer-TAD. Journal of Chemical Information and Modeling 2022, 62 (4) , 890-902. https://doi.org/10.1021/acs.jcim.1c01197EI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Alberto Baiardi, Stephanie A. Grimmel, Miguel Steiner, Paul L. Türtscher, Jan P. Unsleber, Thomas Weymuth, Markus Reiher. Expansive Quantum Mechanical Exploration of Chemical Reaction Paths. Accounts of Chemical Research 2022, 55 (1) , 35-43. https://doi.org/10.1021/acs.accounts.1c00472SCI升级版 化学1区SCI基础版 化学1区IF 16.4
- Craig Waitt, Audrey R. Miles, William F. Schneider. Adsorbate Free Energies from DFT-Derived Translational Energy Landscapes. The Journal of Physical Chemistry C 2021, 125 (37) , 20331-20342. https://doi.org/10.1021/acs.jpcc.1c05917EI检索SCI升级版 化学3区SCI基础版 化学2区IF 3.3SWJTU A++
- Victoria P. Barber, William H. Green, Jesse H. Kroll. Screening for New Pathways in Atmospheric Oxidation Chemistry with Automated Mechanism Generation. The Journal of Physical Chemistry A 2021, 125 (31) , 6772-6788. https://doi.org/10.1021/acs.jpca.1c04297EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Robin J. Shannon, Emilio Martínez-Núñez, Dmitrii V. Shalashilin, David R. Glowacki. ChemDyME: Kinetically Steered, Automated Mechanism Generation through Combined Molecular Dynamics and Master Equation Calculations. Journal of Chemical Theory and Computation 2021, 17 (8) , 4901-4912. https://doi.org/10.1021/acs.jctc.1c00335SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Christoph Brunken, Markus Reiher. Automated Construction of Quantum–Classical Hybrid Models. Journal of Chemical Theory and Computation 2021, 17 (6) , 3797-3813. https://doi.org/10.1021/acs.jctc.1c00178SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Christopher Robertson, Ross Hyland, Andrew J. D. Lacey, Sebastian Havens, Scott Habershon. Identifying Barrierless Mechanisms for Benzene Formation in the Interstellar Medium Using Permutationally Invariant Reaction Discovery. Journal of Chemical Theory and Computation 2021, 17 (4) , 2307-2322. https://doi.org/10.1021/acs.jctc.1c00046SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Thijs Stuyver, Sason Shaik. Promotion Energy Analysis Predicts Reaction Modes: Nucleophilic and Electrophilic Aromatic Substitution Reactions. Journal of the American Chemical Society 2021, 143 (11) , 4367-4378. https://doi.org/10.1021/jacs.1c00307EI检索SCI升级版 化学1区SCI基础版 化学1区IF 14.4SWJTU A++
- Timur Gimadiev, Ramil Nugmanov, Dinar Batyrshin, Timur Madzhidov, Satoshi Maeda, Pavel Sidorov, Alexandre Varnek. Combined Graph/Relational Database Management System for Calculated Chemical Reaction Pathway Data. Journal of Chemical Information and Modeling 2021, 61 (2) , 554-559. https://doi.org/10.1021/acs.jcim.0c01280EI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Ali Hussain Motagamwala, James A. Dumesic. Microkinetic Modeling: A Tool for Rational Catalyst Design. Chemical Reviews 2021, 121 (2) , 1049-1076. https://doi.org/10.1021/acs.chemrev.0c00394EI检索SCI升级版 化学1区SCI基础版 化学1区IF 51.4
- Yu-hong Lam, Yuriy Abramov, Ravi S. Ananthula, Jennifer M. Elward, Lori R. Hilden, Sten O. Nilsson Lill, Per-Ola Norrby, Antonio Ramirez, Edward C. Sherer, Jason Mustakis, Gerald J. Tanoury. Applications of Quantum Chemistry in Pharmaceutical Process Development: Current State and Opportunities. Organic Process Research & Development 2020, 24 (8) , 1496-1507. https://doi.org/10.1021/acs.oprd.0c00222EI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.1
- Christoph Brunken, Markus Reiher. Self-Parametrizing System-Focused Atomistic Models. Journal of Chemical Theory and Computation 2020, 16 (3) , 1646-1665. https://doi.org/10.1021/acs.jctc.9b00855SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Sebastian Dohm, Markus Bursch, Andreas Hansen, Stefan Grimme. Semiautomated Transition State Localization for Organometallic Complexes with Semiempirical Quantum Chemical Methods. Journal of Chemical Theory and Computation 2020, 16 (3) , 2002-2012. https://doi.org/10.1021/acs.jctc.9b01266SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Marco Foscato, Vidar R. Jensen. Automated in Silico Design of Homogeneous Catalysts. ACS Catalysis 2020, 10 (3) , 2354-2377. https://doi.org/10.1021/acscatal.9b04952EI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.3
- Pei-Lin Kang, Cheng Shang, Zhi-Pan Liu. Glucose to 5-Hydroxymethylfurfural: Origin of Site-Selectivity Resolved by Machine Learning Based Reaction Sampling. Journal of the American Chemical Society 2019, 141 (51) , 20525-20536. https://doi.org/10.1021/jacs.9b11535EI检索SCI升级版 化学1区SCI基础版 化学1区IF 14.4SWJTU A++
- Eric D. Hermes, Khachik Sargsyan, Habib N. Najm, Judit Zádor. Accelerated Saddle Point Refinement through Full Exploitation of Partial Hessian Diagonalization. Journal of Chemical Theory and Computation 2019, 15 (11) , 6536-6549. https://doi.org/10.1021/acs.jctc.9b00869SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Valerio Rizzi, Dan Mendels, Emilia Sicilia, Michele Parrinello. Blind Search for Complex Chemical Pathways Using Harmonic Linear Discriminant Analysis. Journal of Chemical Theory and Computation 2019, 15 (8) , 4507-4515. https://doi.org/10.1021/acs.jctc.9b00358SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Sebastian Matera, William F. Schneider, Andreas Heyden, Aditya Savara. Progress in Accurate Chemical Kinetic Modeling, Simulations, and Parameter Estimation for Heterogeneous Catalysis. ACS Catalysis 2019, 9 (8) , 6624-6647. https://doi.org/10.1021/acscatal.9b01234EI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.3
- Dmitrij Rappoport, Alán Aspuru-Guzik. Predicting Feasible Organic Reaction Pathways Using Heuristically Aided Quantum Chemistry. Journal of Chemical Theory and Computation 2019, 15 (7) , 4099-4112. https://doi.org/10.1021/acs.jctc.9b00126SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Jin Woo Kim, Yeonjoon Kim, Kyung Yup Baek, Kyunghoon Lee, Woo Youn Kim. Performance of ACE-Reaction on 26 Organic Reactions for Fully Automated Reaction Network Construction and Microkinetic Analysis. The Journal of Physical Chemistry A 2019, 123 (22) , 4796-4805. https://doi.org/10.1021/acs.jpca.9b02161EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Stefan Grimme. Exploration of Chemical Compound, Conformer, and Reaction Space with Meta-Dynamics Simulations Based on Tight-Binding Quantum Chemical Calculations. Journal of Chemical Theory and Computation 2019, 15 (5) , 2847-2862. https://doi.org/10.1021/acs.jctc.9b00143SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Idil Ismail, Holly B. V. A. Stuttaford-Fowler, Curtis Ochan Ashok, Christopher Robertson, Scott Habershon. Automatic Proposal of Multistep Reaction Mechanisms using a Graph-Driven Search. The Journal of Physical Chemistry A 2019, 123 (15) , 3407-3417. https://doi.org/10.1021/acs.jpca.9b01014EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Satoshi Maeda, Yu Harabuchi. On Benchmarking of Automated Methods for Performing Exhaustive Reaction Path Search. Journal of Chemical Theory and Computation 2019, 15 (4) , 2111-2115. https://doi.org/10.1021/acs.jctc.8b01182SCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Pedro J. Sánchez Gómez, Mauricio Suárez. Plurality and identity: on the educational relations between chemistry and physics. Chemistry Education Research and Practice 2025, https://doi.org/10.1039/D4RP00288ASCI升级版 教育学2区SCI基础版 化学4区IF 2.6
- Philippe Gantzer, Ruben Staub, Yu Harabuchi, Satoshi Maeda, Alexandre Varnek. Chemography‐guided analysis of a reaction path network for ethylene hydrogenation with a model Wilkinson's catalyst. Molecular Informatics 2025, 44 (1) https://doi.org/10.1002/minf.202400063EI检索SCI升级版 医学4区SCI基础版 医学3区IF 2.8SWJTU A
- Seonghwan Kim, Jeheon Woo, Woo Youn Kim. Diffusion-based generative AI for exploring transition states from 2D molecular graphs. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-023-44629-6SCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Miguel Steiner, Markus Reiher. A human-machine interface for automatic exploration of chemical reaction networks. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-47997-9SCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Katja-Sophia Csizi, Miguel Steiner, Markus Reiher. Nanoscale chemical reaction exploration with a quantum magnifying glass. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-49594-2SCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Basudev Maity, Mitsuo Shoji, Fangjia Luo, Takanori Nakane, Satoshi Abe, Shigeki Owada, Jungmin Kang, Kensuke Tono, Rie Tanaka, Thuc Toan Pham, Mariko Kojima, Yuki Hishikawa, Junko Tanaka, Jiaxin Tian, Misaki Nagama, Taiga Suzuki, Hiroki Noya, Yuto Nakasuji, Asuka Asanuma, Xinchen Yao, So Iwata, Yasuteru Shigeta, Eriko Nango, Takafumi Ueno. Real-time observation of a metal complex-driven reaction intermediate using a porous protein crystal and serial femtosecond crystallography. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-49814-9SCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Jonathan P. Mailoa, Xin Li, Shengyu Zhang. 3T-VASP: fast ab-initio electrochemical reactor via multi-scale gradient energy minimization. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-54453-1SCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Nils van Staalduinen, Christoph Bannwarth. MolBar: a molecular identifier for inorganic and organic molecules with full support of stereoisomerism. Digital Discovery 2024, 3 (11) , 2298-2319. https://doi.org/10.1039/D4DD00208CIF 6.2
- Thijs Stuyver. TS‐tools: Rapid and automated localization of transition states based on a textual reaction SMILES input. Journal of Computational Chemistry 2024, 45 (27) , 2308-2317. https://doi.org/10.1002/jcc.27374EI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.4SWJTU A++
- Raquel J. Rama, Ainara Nova, M. Carmen Nicasio. Microkinetic Model as a Crucial Tool for Understanding Homogeneous Catalysis. ChemCatChem 2024, 16 (17) https://doi.org/10.1002/cctc.202400224EI检索SCI升级版 化学3区SCI基础版 化学2区IF 3.8SWJTU A++
- Khaled Kahouli, Stefaan Simon Pierre Hessmann, Klaus-Robert Müller, Shinichi Nakajima, Stefan Gugler, Niklas Wolf Andreas Gebauer. Molecular relaxation by reverse diffusion with time step prediction. Machine Learning: Science and Technology 2024, 5 (3) , 035038. https://doi.org/10.1088/2632-2153/ad652cEI检索SCI升级版 物理与天体物理2区IF 6.3
- Luís P. Viegas, Breno R.L. Galvão. With a little help from our (AI) friend: A general transition state sampling method for tropospheric hydrogen abstraction reactions. Atmospheric Environment 2024, 328 , 120515. https://doi.org/10.1016/j.atmosenv.2024.120515EI检索SCI升级版 环境科学与生态学2区SCI基础版 环境科学与生态学2区IF 4.2
- Thomas Weymuth, Jan P. Unsleber, Paul L. Türtscher, Miguel Steiner, Jan-Grimo Sobez, Charlotte H. Müller, Maximilian Mörchen, Veronika Klasovita, Stephanie A. Grimmel, Marco Eckhoff, Katja-Sophia Csizi, Francesco Bosia, Moritz Bensberg, Markus Reiher. SCINE—Software for chemical interaction networks. The Journal of Chemical Physics 2024, 160 (22) https://doi.org/10.1063/5.0206974EI检索SCI升级版 化学2区SCI基础版 化学3区IF 3.1SWJTU A++
- Daniele Padula. A Computational Perspective on the Reactivity of π ‐spacers in Self‐Immolative Elimination Reactions. Chemistry – An Asian Journal 2024, 19 (7) https://doi.org/10.1002/asia.202400010EI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.5
- G. Ya. Gerasimov, V. Yu. Levashov. Kinetic Models of Combustion of Kerosene. Journal of Engineering Physics and Thermophysics 2024, 97 (2) , 506-524. https://doi.org/10.1007/s10891-024-02918-xEI检索IF 0.6
- W.M.C. Sameera, Yosuke Sumiya, Bastian Bjerkem Skjelstad, Satoshi Maeda. Automated Mechanism Discovery. 2024, 454-484. https://doi.org/10.1016/B978-0-12-821978-2.00003-9
- Thomas Weymuth, Markus Reiher. Heuristics and Uncertainty Quantification in Rational and Inverse Compound and Catalyst Design. 2024, 485-495. https://doi.org/10.1016/B978-0-12-821978-2.00007-6
- Valeria Butera. Density functional theory methods applied to homogeneous and heterogeneous catalysis: a short review and a practical user guide. Physical Chemistry Chemical Physics 2024, 136 https://doi.org/10.1039/D4CP00266KEI检索SCI升级版 化学3区SCI基础版 化学3区IF 2.9SWJTU A++
- Chenru Duan, Yuanqi Du, Haojun Jia, Heather J. Kulik. Accurate transition state generation with an object-aware equivariant elementary reaction diffusion model. Nature Computational Science 2023, 3 (12) , 1045-1055. https://doi.org/10.1038/s43588-023-00563-7EI检索IF 12.0
- Hiroki Hayashi, Satoshi Maeda, Tsuyoshi Mita. Quantum chemical calculations for reaction prediction in the development of synthetic methodologies. Chemical Science 2023, 14 (42) , 11601-11616. https://doi.org/10.1039/D3SC03319HEI检索SCI升级版 化学1区SCI基础版 化学1区IF 7.6
- Kyunghoon Lee, Jun Hyeong Kim, Woo Youn Kim. pyMCD: Python package for searching transition states via the multicoordinate driven method. Computer Physics Communications 2023, 291 , 108831. https://doi.org/10.1016/j.cpc.2023.108831EI检索SCI升级版 物理与天体物理2区SCI基础版 物理2区IF 7.2SWJTU A++
- Qiyuan Zhao, Brett M. Savoie. Deep reaction network exploration of glucose pyrolysis. Proceedings of the National Academy of Sciences 2023, 120 (34) https://doi.org/10.1073/pnas.2305884120SCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 9.4SWJTU A++
- Mikael Kuwahara, Yu Harabuchi, Satoshi Maeda, Jun Fujima, Keisuke Takahashi. Searching chemical action and network (SCAN): an interactive chemical reaction path network platform. Digital Discovery 2023, 2 (4) , 1104-1111. https://doi.org/10.1039/D3DD00026EIF 6.2
- G. Ya. Gerasimov, V. Yu. Levashov. Kinetic Models of Gasoline Combustion. Russian Journal of Physical Chemistry B 2023, 17 (4) , 923-935. https://doi.org/10.1134/S1990793123040231SCI升级版 化学4区SCI基础版 化学4区IF 1.4SWJTU A
- Г. Я. Герасимов, В. Ю. Левашов. Кинетические модели горения бензина. Химическая физика 2023, 42 (8) , 12-26. https://doi.org/10.31857/S0207401X23080046SWJTU A
- Mohamed Ateia, Gabriel Sigmund, Michael J. Bentel, John W. Washington, Adelene Lai, Nathaniel H. Merrill, Zhanyun Wang. Integrated data-driven cross-disciplinary framework to prevent chemical water pollution. One Earth 2023, 6 (8) , 952-963. https://doi.org/10.1016/j.oneear.2023.07.001SCI升级版 环境科学与生态学1区IF 15.1
- Rui Xu, Jan Meisner, Alexander M. Chang, Keiran C. Thompson, Todd J. Martínez. First principles reaction discovery: from the Schrodinger equation to experimental prediction for methane pyrolysis. Chemical Science 2023, 14 (27) , 7447-7464. https://doi.org/10.1039/D3SC01202FEI检索SCI升级版 化学1区SCI基础版 化学1区IF 7.6
- Katja‐Sophia Csizi, Markus Reiher. Universal QM / MM approaches for general nanoscale applications. WIREs Computational Molecular Science 2023, 13 (4) https://doi.org/10.1002/wcms.1656
- Alessandra Toniato, Jan P. Unsleber, Alain C. Vaucher, Thomas Weymuth, Daniel Probst, Teodoro Laino, Markus Reiher. Quantum chemical data generation as fill-in for reliability enhancement of machine-learning reaction and retrosynthesis planning. Digital Discovery 2023, 2 (3) , 663-673. https://doi.org/10.1039/D3DD00006KIF 6.2
- Satoshi Maeda, Yu Harabuchi, Hiroki Hayashi, Tsuyoshi Mita. Toward Ab Initio Reaction Discovery Using the Artificial Force Induced Reaction Method. Annual Review of Physical Chemistry 2023, 74 (1) , 287-311. https://doi.org/10.1146/annurev-physchem-102822-101025EI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.7
- Wataru Matsuoka, Yu Harabuchi, Yuuya Nagata, Satoshi Maeda. Highly chemoselective ligands for Suzuki–Miyaura cross-coupling reaction based on virtual ligand-assisted screening. Organic & Biomolecular Chemistry 2023, 21 (15) , 3132-3142. https://doi.org/10.1039/D3OB00398AEI检索SCI升级版 化学3区SCI基础版 化学3区IF 2.9
- Lukas Krep, Felix Schmalz, Florian Solbach, Leonid Komissarov, Thomas Nevolianis, Wassja A. Kopp, Toon Verstraelen, Kai Leonhard. A Reactive Molecular Dynamics Study of Chlorinated Organic Compounds. Part II: A ChemTraYzer Study of Chlorinated Dibenzofuran Formation and Decomposition Processes. ChemPhysChem 2023, 24 (7) https://doi.org/10.1002/cphc.202200783EI检索SCI升级版 化学3区SCI基础版 化学3区IF 2.3SWJTU A+
- Moritz Bensberg, Markus Reiher. Concentration‐Flux‐Steered Mechanism Exploration with an Organocatalysis Application. Israel Journal of Chemistry 2023, 8 https://doi.org/10.1002/ijch.202200123SCI升级版 化学4区SCI基础版 化学3区IF 2.3
- Jan P. Unsleber, Hongbin Liu, Leopold Talirz, Thomas Weymuth, Maximilian Mörchen, Adam Grofe, Dave Wecker, Christopher J. Stein, Ajay Panyala, Bo Peng, Karol Kowalski, Matthias Troyer, Markus Reiher. High-throughput ab initio reaction mechanism exploration in the cloud with automated multi-reference validation. The Journal of Chemical Physics 2023, 158 (8) https://doi.org/10.1063/5.0136526EI检索SCI升级版 化学2区SCI基础版 化学3区IF 3.1SWJTU A++
- Yoshifumi Nishimura, Hiromi Nakai. Species-selective nanoreactor molecular dynamics simulations based on linear-scaling tight-binding quantum chemical calculations. The Journal of Chemical Physics 2023, 158 (5) https://doi.org/10.1063/5.0132573EI检索SCI升级版 化学2区SCI基础版 化学3区IF 3.1SWJTU A++
- Choon Wee Kee. Molecular Understanding and Practical In Silico Catalyst Design in Computational Organocatalysis and Phase Transfer Catalysis—Challenges and Opportunities. Molecules 2023, 28 (4) , 1715. https://doi.org/10.3390/molecules28041715SCI升级版 化学2区SCI基础版 化学3区IF 4.2SWJTU A+
- Pablo Ramos‐Sánchez, Jeremy N. Harvey, José A. Gámez. An automated method for graph‐based chemical space exploration and transition state finding. Journal of Computational Chemistry 2023, 44 (1) , 27-42. https://doi.org/10.1002/jcc.27011EI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.4SWJTU A++
- Zhengkai Tu, Thijs Stuyver, Connor W. Coley. Predictive chemistry: machine learning for reaction deployment, reaction development, and reaction discovery. Chemical Science 2023, 14 (2) , 226-244. https://doi.org/10.1039/D2SC05089GEI检索SCI升级版 化学1区SCI基础版 化学1区IF 7.6
- Yu Harabuchi, Hiroki Hayashi, Hideaki Takano, Tsuyoshi Mita, Satoshi Maeda. Oxidation and Reduction Pathways in the Knowles Hydroamination via a Photoredox‐Catalyzed Radical Reaction**. Angewandte Chemie International Edition 2023, 62 (1) https://doi.org/10.1002/anie.202211936EI检索SCI升级版 化学1区SCI基础版 化学1区IF 16.1SWJTU A++
- Yu Harabuchi, Hiroki Hayashi, Hideaki Takano, Tsuyoshi Mita, Satoshi Maeda. Oxidation and Reduction Pathways in the Knowles Hydroamination via a Photoredox‐Catalyzed Radical Reaction**. Angewandte Chemie 2023, 135 (1) https://doi.org/10.1002/ange.202211936
- Mingjian Wen, Evan Walter Clark Spotte-Smith, Samuel M. Blau, Matthew J. McDermott, Aditi S. Krishnapriyan, Kristin A. Persson. Chemical reaction networks and opportunities for machine learning. Nature Computational Science 2023, 3 (1) , 12-24. https://doi.org/10.1038/s43588-022-00369-zEI检索IF 12.0
- Siyuan Gong, Yutong Wang, Yajie Tian, Li Wang, Guozhu Liu. Rapid enthalpy prediction of transition states using molecular graph convolutional network. AIChE Journal 2023, 69 (1) https://doi.org/10.1002/aic.17269EI检索SCI升级版 工程技术3区SCI基础版 工程技术3区IF 3.5
- Rocío Durán, Nery Villegas-Escobar, Daniela E. Ortega, Ricardo A. Matute. The diabatic model of intermediate stabilization for reaction mechanism analysis: a link to valence bond and Marcus theories. 2023, 347-375. https://doi.org/10.1016/B978-0-32-390257-1.00018-8
- M. Podewitz. Towards predictive computational catalysis – a case study of olefin metathesis with Mo imido alkylidene N-heterocyclic carbene catalysts. 2022, 1-23. https://doi.org/10.1039/9781839169342-00001
- . Exploration Methods. 2022, 17-68. https://doi.org/10.1039/9781839167744-00017
- Cyrille Lavigne, Gabe Gomes, Robert Pollice, Alán Aspuru-Guzik. Guided discovery of chemical reaction pathways with imposed activation. Chemical Science 2022, 13 (46) , 13857-13871. https://doi.org/10.1039/D2SC05135DEI检索SCI升级版 化学1区SCI基础版 化学1区IF 7.6
- Tobias M. Pazdera, Johannes Wenz, Matthias Olzmann. The unimolecular decomposition of dimethoxymethane: channel switching as a function of temperature and pressure. Faraday Discussions 2022, 238 , 665-681. https://doi.org/10.1039/D2FD00039CEI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.3
- Francesco Bosia, Thomas Weymuth, Markus Reiher. Ultra‐fast spectroscopy for high‐throughput and interactive quantum chemistry. International Journal of Quantum Chemistry 2022, 122 (19) https://doi.org/10.1002/qua.26966EI检索SCI升级版 化学3区SCI基础版 化学4区IF 2.3
了解这些指标
Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.
Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.
The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.
推荐文章
- Chemoton 2.0：化学反应网络的自主探索
GFN2-xTB—一种具有多极静电和密度相关色散贡献的精确且广泛参数化的自洽紧束缚量子化学方法
Context-Driven Exploration of Complex Chemical Reaction Networks
Expansive Quantum Mechanical Exploration of Chemical Reaction Paths
Pathfinder─Navigating and Analyzing Chemical Reaction Networks with an Efficient Graph-Based Approach
Sponsored Content
Learn everything you need to know to operate HPLCs and/or GCs, develop methods and troubleshoot.
摘要
Figure 1
Figure 1. General strategies for the exploration of PESs. Left: local curvature information on the PES is exploited to identify TSs and products. Middle: through the application of heuristics new intermediates are identified. Right: intermediates and TSs are explored interactively. In the two latter cases of heuristics-based and interactive explorations, pathways need to be refined a posteriori to obtain MEPs. An efficient exploration protocol may combine strategies from different classes.
Figure 2
Figure 2. Schematic course of a typical quantum chemical calculation. (a) Traditionally, the most time-intensive step is the computation step on the CPU. (b) With increasing CPU power, the duration of quantum chemical calculations decreases for a fixed system size and some given electronic structure model. (c) For a quasi-instantaneous calculation, the most time-intensive step is now no longer the computation itself, but the bottleneck becomes the setup and the analysis of the results.
Figure 3
Figure 3. Main components of a real-time quantum chemistry framework. The central element is the molecular structure under study (center) that is displayed (top right) to the operator. The operator can move atoms and experience the effects of his manipulations with a computer mouse or a haptic device (top left). Single-point calculations run continuously in the background (bottom) and deliver the nuclear forces underlying the reactivity exploration as well as other relevant quantum chemical properties.
Figure 4
Figure 4. Combined strengths of three classes of exploration strategies result in a universally applicable exploration protocol.
References
This article references 262 other publications.
- 1Masters, C. Homogeneous Transition-Metal Catalysis: A Gentle Art, 1st ed.; Springer, 2011.There is no corresponding record for this reference.
- 2Vinu, R.; Broadbelt, L. J. Unraveling Reaction Pathways and Specifying Reaction Kinetics for Complex Systems. Annu. Rev. Chem. Biomol. Eng. 2012, 3, 29– 54, DOI: 10.1146/annurev-chembioeng-062011-0811082https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1GmtbnK&md5=c4ba8d6755e934d6a78993f8e67a6b85Unraveling reaction pathways and specifying reaction kinetics for complex systemsVinu, R.; Broadbelt, Linda J.Annual Review of Chemical and Biomolecular Engineering (2012), 3 (), 29-54CODEN: ARCBCY; ISSN:1947-5438. (Annual Reviews Inc.)A review. Many natural and industrial processes involve a complex set of competing reactions that include several different species. Detailed kinetic modeling of such systems can shed light on the important pathways involved in various transformations and therefore can be used to optimize the process conditions for the desired product compn. and properties. This review focuses on elucidating the various components involved in modeling the kinetics of pyrolysis and oxidn. of polymers. The elementary free radical steps that constitute the chain reaction mechanism of gas-phase/nonpolar liq.-phase processes are outlined. Specification of the rate coeffs. of the various reaction families, which is central to the theme of kinetics, is described. Construction of the reaction network on the basis of the types of end groups and reactive moieties in a polymer chain is discussed. Modeling frameworks based on the method of moments and kinetic Monte Carlo are evaluated using illustrations. Finally, the prospects and challenges in modeling biomass conversion are addressed.
- 4Jorgensen, W. L. The Many Roles of Computation in Drug Discovery. Science 2004, 303, 1813– 1818, DOI: 10.1126/science.10963614https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXitFehu7w%253D&md5=77b2fac63e750ca7cdc7e4f35654549aThe Many Roles of Computation in Drug DiscoveryJorgensen, William L.Science (Washington, DC, United States) (2004), 303 (5665), 1813-1818CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review. An overview is given on the diverse uses of computational chem. in drug discovery. Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for detg. protein-ligand binding.
- 5Valdez, C. E.; Morgenstern, A.; Eberhart, M. E.; Alexandrova, A. N. Predictive Methods for Computational Metalloenzyme Redesign – a Test Case with Carboxypeptidase A. Phys. Chem. Chem. Phys. 2016, 18, 31744– 31756, DOI: 10.1039/C6CP02247B5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFCrsbbO&md5=b11bfcb0cc2fec4149ad6f9fc28ffa66Predictive methods for computational metalloenzyme redesign - a test case with carboxypeptidase AValdez, Crystal E.; Morgenstern, Amanda; Eberhart, Mark E.; Alexandrova, Anastassia N.Physical Chemistry Chemical Physics (2016), 18 (46), 31744-31756CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Computational metalloenzyme design is a multi-scale problem. It requires treating the metal coordination quantum mech., extensive sampling of the protein backbone, and addnl. accounting for the polarization of the active site by both the metal cation and the surrounding protein (a phenomenon called electrostatic preorganization). We bring together a combination of theor. methods that jointly offer these desired qualities: QM/DMD for mixed quantum-classical dynamic sampling, quantum theory of atoms in mols. (QTAIM) for the assessment of electrostatic preorganization, and D. Functional Theory (DFT) for mechanistic studies. Within this suite of principally different methods, there are both complementarity of capabilities and cross-validation. Using these methods, predictions can be made regarding the relative activities of related enzymes, as we show on the native Zn2+-dependent carboxypeptidase A (CPA), and its mutant proteins, which are hypothesized to hydrolyze modified substrates. For the native CPA, we replicated the catalytic mechanism and the rate in close agreement with the expt., giving validity to the QM/DMD predicted structure, the DFT mechanism, and the QTAIM assessment of catalytic activity. For most sequences of the modified substrate and tried CPA mutants, substantially worsened activity is predicted. However, for the substrate mutant that contains Asp instead of Phe at the C-terminus, one CPA mutant exhibits a reasonable activity, as predicted across the theor. methods. CPA is a well-studied system, and here it serves as a testing ground for the offered methods.
- 6Honkala, K.; Hellman, A.; Remediakis, I. N.; Logadottir, A.; Carlsson, A.; Dahl, S.; Christensen, C. H.; Nørskov, J. K. Ammonia Synthesis from First-Principles Calculations. Science 2005, 307, 555– 5586https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslOjuw%253D%253D&md5=4c6066f84d200c9c587b6dd1dcd3b0bfAmmonia Synthesis from First-Principles CalculationsHonkala, K.; Hellman, A.; Remediakis, I. N.; Logadottir, A.; Carlsson, A.; Dahl, S.; Christensen, C. H.; Norskov, J. K.Science (Washington, DC, United States) (2005), 307 (5709), 555-558CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The rate of ammonia synthesis over a nanoparticle ruthenium catalyst can be calcd. directly on the basis of a quantum chem. treatment of the problem using d. functional theory. We compared the results to measured rates over a ruthenium catalyst supported on magnesium aluminum spinel. When the size distribution of ruthenium particles measured by transmission electron microscopy was used as the link between the catalyst material and the theor. treatment, the calcd. rate was within a factor of 3 to 20 of the exptl. rate. This offers hope for computer-based methods in the search for catalysts.
- 7Medford, A. J.; Wellendorff, J.; Vojvodic, A.; Studt, F.; Abild-Pedersen, F.; Jacobsen, K. W.; Bligaard, T.; Nørskov, J. K. Assessing the Reliability of Calculated Catalytic Ammonia Synthesis Rates. Science 2014, 345, 197– 200, DOI: 10.1126/science.12534867https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFWjtLvK&md5=af3416666eeec422dd8f7c7543b9488eAssessing the reliability of calculated catalytic ammonia synthesis ratesMedford, Andrew J.; Wellendorff, Jess; Vojvodic, Aleksandra; Studt, Felix; Abild-Pedersen, Frank; Jacobsen, Karsten W.; Bligaard, Thomas; Norskov, Jens K.Science (Washington, DC, United States) (2014), 345 (6193), 197-200CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)We introduce a general method for estg. the uncertainty in calcd. materials properties based on d. functional theory calcns. We illustrate the approach for a calcn. of the catalytic rate of ammonia synthesis over a range of transition-metal catalysts. The correlation between errors in d. functional theory calcns. is shown to play an important role in reducing the predicted error on calcd. rates. Uncertainties depend strongly on reaction conditions and catalyst material, and the relative rates between different catalysts are considerably better described than the abs. rates. We introduce an approach for incorporating uncertainty when searching for improved catalysts by evaluating the probability that a given catalyst is better than a known std.
- 8Matera, S.; Maestri, M.; Cuoci, A.; Reuter, K. Predictive-Quality Surface Reaction Chemistry in Real Reactor Models: Integrating First-Principles Kinetic Monte Carlo Simulations into Computational Fluid Dynamics. ACS Catal. 2014, 4, 4081– 4092, DOI: 10.1021/cs501154e8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs12kurjF&md5=e0f052a4546ccf857b9e898b8d08825bPredictive-Quality Surface Reaction Chemistry in Real Reactor Models: Integrating First-Principles Kinetic Monte Carlo Simulations into Computational Fluid DynamicsMatera, Sebastian; Maestri, Matteo; Cuoci, Alberto; Reuter, KarstenACS Catalysis (2014), 4 (11), 4081-4092CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)We present a numerical framework to integrate first-principles kinetic Monte Carlo (1p-kMC) based microkinetic models into the powerful computational fluid dynamics (CFD) package CatalyticFoam. This allows for the simultaneous account of a predictive-quality surface reaction kinetics inside an explicitly described catalytic reactor geometry. Crucial means toward an efficient and stable implementation are the exploitation of the disparate time scales of surface chem. and gas-phase transport, as well as the reliable interpolation of irregularly gridded 1p-kMC data by means of an error-based modified Shepard approach. We illustrate the capabilities of the framework using the CO oxidn. at Pd(100) and RuO2(110) model catalysts in different reactor configurations and fluid dynamic conditions as showcases. These showcases underscore both the necessity and value of having reliable treatments of the surface chem. and flow inside integrated multiscale catalysis simulations when aiming at an at.-scale understanding of the catalytic function in near-ambient environments. Our examples highlight how intricately this function is affected by specifics of the reactor geometry and heat dissipation channels on the one end, and on the other end by characteristics of the intrinsic catalytic activity that are only captured by treatments beyond prevalent mean-field rate equations.
- 9Reuter, K. Ab Initio Thermodynamics and First-Principles Microkinetics for Surface Catalysis. Catal. Lett. 2016, 146, 541– 563, DOI: 10.1007/s10562-015-1684-39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xps1CnsQ%253D%253D&md5=352bd644b8fabaf14fc7e70d0f29b5a0Ab Initio Thermodynamics and First-Principles Microkinetics for Surface CatalysisReuter, KarstenCatalysis Letters (2016), 146 (3), 541-563CODEN: CALEER; ISSN:1011-372X. (Springer)A review; ab initio thermodn. and first-principles microkinetic simulations have become std. tools in research on model catalysts. Complementing dedicated in situ expts. these techniques contribute to our evolving mechanistic understanding, in particular of a reaction-induced dynamical evolution of the working catalyst surface. This topical review surveys the methodol. foundations and ongoing developments of both techniques, and specifically illustrates the type of insights they provide in the context of in situ model catalyst studies. This insight points at substantial deviations from the std. picture that analyzes catalytic function merely in terms of properties of and processes at active sites as they emerge from a crystal lattice truncation of the nominal catalyst bulk material.
- 10Baxter, E. T.; Ha, M.-A.; Cass, A. C.; Alexandrova, A. N.; Anderson, S. L. Ethylene Dehydrogenation on Pt4,7,8 Clusters on Al2O3: Strong Cluster Size Dependence Linked to Preferred Catalyst Morphologies. ACS Catal. 2017, 7, 3322– 3335, DOI: 10.1021/acscatal.7b0040910https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltVSqsbc%253D&md5=d1944c4c7de19d6e44ea69ac739c458dEthylene Dehydrogenation on Pt4,7,8 Clusters on Al2O3: Strong Cluster Size Dependence Linked to Preferred Catalyst MorphologiesBaxter, Eric T.; Ha, Mai-Anh; Cass, Ashley C.; Alexandrova, Anastassia N.; Anderson, Scott L.ACS Catalysis (2017), 7 (5), 3322-3335CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Catalytic dehydrogenation of ethylene on size-selected Ptn (n = 4, 7, 8) clusters deposited on the surface of Al2O3 was studied exptl. and theor. Clusters were mass-selected, deposited on the alumina support, and probed by a combination of low energy ion scattering, temp.-programmed desorption and reaction of C2D4 and D2, XPS, d. functional theory, and statistical mech. theory. Pt7 is identified as the most catalytically active cluster, while Pt4 and Pt8 exhibit comparable activities. The higher activity can be related to the cluster structure and particularly to the distribution of cluster morphologies accessible at the temps. and coverage with ethylene in catalytic conditions. Specifically, while Pt7 and Pt8 on alumina have very similar prismatic global min. geometries, Pt7 at higher temps. also has access to single-layer isomers, which become more and more predominant in the cluster catalyst ensemble upon increasing ethylene coverage. Single-layer isomers feature greater charge transfer from the support and more binding sites that activate ethylene for dehydrogenation rather than hydrogenation or desorption. Size-dependent susceptibility to coking and deactivation was also studied. Results show that size-dependent catalytic activity of clusters is not a simple property of single cluster geometry but the av. over a statistical ensemble at relevant conditions.
- 11Ha, M.-A.; Baxter, E. T.; Cass, A. C.; Anderson, S. L.; Alexandrova, A. N. Boron Switch for Selectivity of Catalytic Dehydrogenation on Size-Selected Pt Clusters on Al2O3. J. Am. Chem. Soc. 2017, 139, 11568– 11575, DOI: 10.1021/jacs.7b0589411https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1GjsbrO&md5=c4fb4ca3671fed66af60f96ac51a86cbBoron Switch for Selectivity of Catalytic Dehydrogenation on Size-Selected Pt Clusters on Al2O3Ha, Mai-Anh; Baxter, Eric T.; Cass, Ashley C.; Anderson, Scott L.; Alexandrova, Anastassia N.Journal of the American Chemical Society (2017), 139 (33), 11568-11575CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Size-selected supported clusters of transition metals can be remarkable and highly tunable catalysts. A particular example is Pt clusters deposited on alumina, which have been shown to dehydrogenate hydrocarbons in a size-specific manner. Pt7, of the three sizes studied, is the most active and, therefore, like many other catalysts, deactivates by coking during reactions in hydrocarbon-rich environments. Using a combination of expt. and theory, we show that nanoalloying Pt7 with boron modifies the alkene-binding affinity to reduce coking. From a fundamental perspective, the comparison of exptl. and theor. results shows the importance of considering not simply the most stable cluster isomer, but rather the ensemble of accessible structures as it changes in response to temp. and reagent coverage.
- 12Ulissi, Z. W.; Medford, A. J.; Bligaard, T.; Nørskov, J. K. To Address Surface Reaction Network Complexity Using Scaling Relations Machine Learning and DFT Calculations. Nat. Commun. 2017, 8, 14621, DOI: 10.1038/ncomms1462112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czjtFamuw%253D%253D&md5=bde19b4dcb6abce90b2ea7ab073e1c6eTo address surface reaction network complexity using scaling relations machine learning and DFT calculationsUlissi Zachary W; Norskov Jens K; Medford Andrew J; Bligaard ThomasNature communications (2017), 8 (), 14621 ISSN:.Surface reaction networks involving hydrocarbons exhibit enormous complexity with thousands of species and reactions for all but the very simplest of chemistries. We present a framework for optimization under uncertainty for heterogeneous catalysis reaction networks using surrogate models that are trained on the fly. The surrogate model is constructed by teaching a Gaussian process adsorption energies based on group additivity fingerprints, combined with transition-state scaling relations and a simple classifier for determining the rate-limiting step. The surrogate model is iteratively used to predict the most important reaction step to be calculated explicitly with computationally demanding electronic structure theory. Applying these methods to the reaction of syngas on rhodium(111), we identify the most likely reaction mechanism. Propagating uncertainty throughout this process yields the likelihood that the final mechanism is complete given measurements on only a subset of the entire network and uncertainty in the underlying density functional theory calculations.
- 13Vereecken, L.; Glowacki, D. R.; Pilling, M. J. Theoretical Chemical Kinetics in Tropospheric Chemistry: Methodologies and Applications. Chem. Rev. 2015, 115, 4063– 4114, DOI: 10.1021/cr500488p13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXmtVWqs7s%253D&md5=75c3bde1b210e3c1555d0c946f8e4976Theoretical Chemical Kinetics in Tropospheric Chemistry: Methodologies and ApplicationsVereecken, Luc; Glowacki, David R.; Pilling, Michael J.Chemical Reviews (Washington, DC, United States) (2015), 115 (10), 4063-4114CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review is presented. Chem. Kinetics in Tropospheric Chem. is studied.
- 14Ludlow, R. F.; Otto, S. Systems Chemistry. Chem. Soc. Rev. 2008, 37, 101– 108, DOI: 10.1039/B611921M14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtVWhtQ%253D%253D&md5=151c83f30396538fccc0ea2f9c016d26Systems chemistryLudlow, R. Frederick; Otto, SijbrenChemical Society Reviews (2008), 37 (1), 101-108CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A tutorial review. The study of complex mixts. of interacting synthetic mols. has historically not received much attention from chemists, even though research into complexity is well established in the neighboring fields. However, with the huge recent interest in systems biol. and the availability of modern anal. techniques this situation is likely to change. In this tutorial review we discuss some of the incentives for developing systems chem. and we highlight the pioneering work in which mol. networks are making a splash. A distinction is made between networks under thermodn. and kinetic control. The former include dynamic combinatorial libraries while the latter involve pseudo-dynamic combinatorial libraries, oscillating reactions and networks of autocatalytic and replicating compds. These studies provide fundamental insights into the organizational principles of mol. networks and how these give rise to emergent properties such as amplification and feedback loops, and may eventually shed light on the origin of life. The knowledge obtained from the study of mol. networks should ultimately enable us to engineer new systems with properties and functions unlike any conventional materials.
- 15Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic Chemistry; Oxford University Press: Oxford, 2001.There is no corresponding record for this reference.
- 17Sameera, W. M. C.; Maeda, S.; Morokuma, K. Computational Catalysis Using the Artificial Force Induced Reaction Method. Acc. Chem. Res. 2016, 49, 763– 773, DOI: 10.1021/acs.accounts.6b0002317https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvFSnsb0%253D&md5=761857a94f5b7c7366b98650d8a42646Computational Catalysis Using the Artificial Force Induced Reaction MethodSameera, W. M. C.; Maeda, Satoshi; Morokuma, KeijiAccounts of Chemical Research (2016), 49 (4), 763-773CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)The artificial force induced reaction (AFIR) method in the global reaction route mapping (GRRM) strategy is an automatic approach to explore all important reaction paths of complex reactions. Most traditional methods in computational catalysis require guess reaction paths. On the other hand, the AFIR approach locates local min. (LMs) and transition states (TSs) of reaction paths without a guess, and therefore finds unanticipated as well as anticipated reaction paths. The AFIR method has been applied for multicomponent org. reactions, such as the aldol reaction, Passerini reaction, Biginelli reaction, and phase-transfer catalysis. In the presence of several reactants, many equil. structures are possible, leading to a no. of reaction pathways. The AFIR method in the GRRM strategy dets. all of the important equil. structures and subsequent reaction paths systematically. As the AFIR search is fully automatic, exhaustive trial-and-error and guess-and-check processes by the user can be eliminated. At the same time, the AFIR search is systematic, and therefore a more accurate and comprehensive description of the reaction mechanism can be detd.The AFIR method has been used for the study of full catalytic cycles and reaction steps in transition metal catalysis, such as cobalt-catalyzed hydroformylation and iron-catalyzed carbon-carbon bond formation reactions in aq. media. Some AFIR applications have targeted the selectivity-detg. step of transition-metal-catalyzed asym. reactions, including stereoselective water-tolerant lanthanide Lewis acid-catalyzed Mukaiyama aldol reactions. In terms of establishing the selectivity of a reaction, systematic sampling of the transition states is crit. In this direction, AFIR is very useful for performing a systematic and automatic detn. of TSs. In the presence of a comprehensive description of the transition states, the selectivity of the reaction can be calcd. more accurately.For relatively large mol. systems, the computational cost of AFIR searches can be reduced by using the ONIOM(QM:QM) or ONIOM(QM:MM) methods. In common practice, d. functional theory (DFT) with a relatively small basis set is used for the high-level calcn., while a semiempirical approach or a force field description is used for the low-level calcn. After approx. LMs and TSs are detd., std. computational methods (e.g., DFT with a large basis set) are used for the full mol. system to det. the true LMs and TSs and to rationalize the reaction mechanism and selectivity of the catalytic reaction.The examples in this Account evidence that the AFIR method is a powerful approach for accurate prediction of the reaction mechanisms and selectivities of complex catalytic reactions. Therefore, the AFIR approach in the GRRM strategy is very useful for computational catalysis.
- 18Hawkins, P. C. D. Conformation Generation: The State of the Art. J. Chem. Inf. Model. 2017, 57, 1747– 1756, DOI: 10.1021/acs.jcim.7b0022118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFagu7bE&md5=776818e66798d1987e015440a28e208eConformation Generation: The State of the ArtHawkins, Paul C. D.Journal of Chemical Information and Modeling (2017), 57 (8), 1747-1756CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The generation of conformations for small mols. is a problem of continuing interest in cheminformatics and computational drug discovery. This review will present an overview of methods used to sample conformational space, focusing on those methods designed for org. mols. commonly of interest in drug discovery. Different approaches to both the sampling of conformational space and the scoring of conformational stability will be compared and contrasted, with an emphasis on those methods suitable for conformer sampling of large nos. of drug-like mols. Particular attention will be devoted to the appropriate utilization of information from exptl. solid-state structures in validating and evaluating the performance of these tools. The review will conclude with some areas worthy of further investigation.
- 19Ohno, K.; Maeda, S. A Scaled Hypersphere Search Method for the Topography of Reaction Pathways on the Potential Energy Surface. Chem. Phys. Lett. 2004, 384, 277– 282, DOI: 10.1016/j.cplett.2003.12.03019https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXksFWguw%253D%253D&md5=d695800fcf7c758ae9e5f6213d187edaA scaled hypersphere search method for the topography of reaction pathways on the potential energy surfaceOhno, Koichi; Maeda, SatoshiChemical Physics Letters (2004), 384 (4-6), 277-282CODEN: CHPLBC; ISSN:0009-2614. (Elsevier Science B.V.)An algorithm for finding pathways to transition states (TS) or dissocn. channels (DC) from equil. structures (EQ) on the potential energy surface (PES) is presented. The pathways around an EQ can be discovered at min. on the scaled hypersphere which would have a const. energy when the potentials are harmonic. Topog. maps including all TS, DC, and EQ were obtained for ab initio PES of H2O and HCHO in the MP2/3-21G level. The present scaled hypersphere search technique in combination with a downhill-walk algorithm enables us to make a topog. anal. of the PES for a given chem. compn.
- 21Maeda, S.; Ohno, K. Global Mapping of Equilibrium and Transition Structures on Potential Energy Surfaces by the Scaled Hypersphere Search Method: Applications to Ab Initio Surfaces of Formaldehyde and Propyne Molecules. J. Phys. Chem. A 2005, 109, 5742– 5753, DOI: 10.1021/jp051316221https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXksl2mtLk%253D&md5=68d94d344ec0774f5313ba93e456ffe3Global Mapping of Equilibrium and Transition Structures on Potential Energy Surfaces by the Scaled Hypersphere Search Method: Applications to ab Initio Surfaces of Formaldehyde and Propyne MoleculesMaeda, Satoshi; Ohno, KoichiJournal of Physical Chemistry A (2005), 109 (25), 5742-5753CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Tech. details of a new global mapping technique for finding equil. (EQ) and transition structures (TS) on potential energy surfaces (PES), the scaled hypersphere search (SHS) method (Ohno, K.; Maeda, S. Chem. Phys. Lett. 2004, 384, 277), are presented. On the basis of a simple principle that reaction pathways are found as anharmonic downward distortions of PES around an EQ point, the reaction pathways can be obtained as energy min. on the scaled hypersphere surface, which would have a const. energy when the potentials are harmonic. Connections of SHS paths between each EQ are very similar to corresponding intrinsic reaction coordinate (IRC) connections. The energy max. along the SHS path reaches a region in close proximity to the TS of the reaction pathway, and the subsequent geometry optimization from the SHS max. structure easily converges to the TS. The SHS method, using the one-after-another algorithm connecting EQ and TS, considerably reduces the multidimensional space to be searched to certain limited regions around the pathways connecting each EQ with the neighboring TS. Applications of the SHS method have been made to ab initio surfaces of formaldehyde and propyne mols. to obtain systematically five EQ and nine TS for formaldehyde and seven EQ and 32 TS for propyne.
- 22Ohno, K.; Maeda, S. Global Reaction Route Mapping on Potential Energy Surfaces of Formaldehyde, Formic Acid, and Their Metal-Substituted Analogues. J. Phys. Chem. A 2006, 110, 8933– 8941, DOI: 10.1021/jp061149l22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XlvVWlsLk%253D&md5=b057c5984bdd877c2a57f80cfe6aa8a6Global Reaction Route Mapping on Potential Energy Surfaces of Formaldehyde, Formic Acid, and Their Metal-Substituted AnaloguesOhno, Koichi; Maeda, SatoshiJournal of Physical Chemistry A (2006), 110 (28), 8933-8941CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Global reaction route mapping of equil. structures, transition structures, and their connections on potential energy surface (PES) has been done for MCHO (M = H, Li, Na, Al, Cu) and HCO2M (M = H, Li). A one-after-another technique based on the scaled hypersphere search method has been successfully applied to exploring unknown chem. structures, transition structures, and reaction pathways for organometallic systems. Upon metal substitution, considerable changes of stable structures, reaction pathways, and relative heights of transition structures have been discovered, though some features are similar among the analogs. Al and Cu atoms were found to behave as very strong scissors to cut the CO double bond in MCHO. Energy profiles of the CO insertion into Li-H and Li-CH3 bonds were found to be very similar, esp. around the structures where the Li atom is not directly connected with the Me group, which indicates little effects of alkyl substitution on the reaction route topol.
- 23Maeda, S.; Ohno, K.; Morokuma, K. Systematic Exploration of the Mechanism of Chemical Reactions: The Global Reaction Route Mapping (GRRM) Strategy Using the ADDF and AFIR Methods. Phys. Chem. Chem. Phys. 2013, 15, 3683– 3701, DOI: 10.1039/c3cp44063j23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXislynsrg%253D&md5=3091bebd5edabab18bdabe51eb001e65Systematic exploration of the mechanism of chemical reactions: the global reaction route mapping (GRRM) strategy using the ADDF and AFIR methodsMaeda, Satoshi; Ohno, Koichi; Morokuma, KeijiPhysical Chemistry Chemical Physics (2013), 15 (11), 3683-3701CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Global reaction route mapping (GRRM), a fully-automated search for all important reaction pathways relevant to a given purpose, from quantum chem. calcns. enables systematic elucidation of complex chem. reaction mechanisms. However, GRRM had previously been limited to very simple systems. This is mainly because such calcns. are highly demanding even in small systems when a brute-force sampling is considered. Hence, the authors have developed two independent but complementary methods: anharmonic downward distortion following (ADDF) and artificial force induced reaction (AFIR) methods. ADDF can follow reaction pathways starting from local min. on the potential energy surface (PES) toward transition structures (TSs) and dissocn. channels. AFIR can find pathways starting from two or more reactants toward TSs for their associative reactions. ADDF searches for A X type isomerization and A X + Y type dissocn. pathways, whereas AFIR finds A + B X (+ Y) type associative pathways. Both follow special paths called the ADDF path and the AFIR path, and these tend to pass through near TSs of corresponding reaction pathways, giving approx. TSs. Such approx. TSs can easily be reoptimized to corresponding true TSs by std. geometry optimizations. From these two methods, the authors proposed practical strategies of GRRM. The GRRM strategies were applied to a variety of chem. systems ranging from thermal- and photochem.-reactions in small systems to organometallic- and enzyme-catalysis, from quantum chem. calcns. In this perspective, the authors present an overview of the GRRM strategies and some results of applications. Their practical usage for systematic prediction is also discussed.
- 24Satoh, H.; Oda, T.; Nakakoji, K.; Uno, T.; Tanaka, H.; Iwata, S.; Ohno, K. Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers. J. Chem. Theory Comput. 2016, 12, 5293– 5308, DOI: 10.1021/acs.jctc.6b0043924https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFOktr%252FF&md5=a395292cdbf67ed58b06748344d48939Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of D-Glucose ConformersSatoh, Hiroko; Oda, Tomohiro; Nakakoji, Kumiyo; Uno, Takeaki; Tanaka, Hiroaki; Iwata, Satoru; Ohno, KoichiJournal of Chemical Theory and Computation (2016), 12 (11), 5293-5308CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)This paper describes approach that is built upon the potential energy surface (PES)-based conformational anal. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search was achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the min. and TS structures by simply taking into account the math. feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equil. (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalcn. anal. of the deduced r-map is interactively carried out using the RMapViewer software the authors have developed. This paper presents computational details of the PES-based conformational anal. and its application to D-glucose. The calcns. were performed for an isolated glucose mol. in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-D-glucose is composed of 201 Equiv and 435 TS conformers and that for β-D-glucose is composed of 202 Equiv and 371 TS conformers. For the postcalcn. anal. of the conformational r-maps by using the RMapViewer software program the authors found multiple min. energy paths (MEPs) between global min. of 1C4 and 4C1 chair conformations. The anal. using RMapViewer allows us to confirm the thermodn. and kinetic predominance of 4C1 conformations; i.e., the potential energy of the global min. of 4C1 is lower than that of 1C4 (thermodn. predominance) and that the highest energy of those of all the TS structures along a route from 4C1 to 1C4 is lower than that of 1C4 to 4C1 (kinetic predominance).
- 25Maeda, S.; Morokuma, K. A Systematic Method for Locating Transition Structures of A+B→X Type Reactions. J. Chem. Phys. 2010, 132, 241102, DOI: 10.1063/1.345790325https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnvFShtLs%253D&md5=9260f723c31e0b78b5677bb4a89f21d7Communications: A systematic method for locating transition structures of A + B → X type reactionsMaeda, Satoshi; Morokuma, KeijiJournal of Chemical Physics (2010), 132 (24), 241102/1-241102/4CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Search for transition structures (TSs) as first-order saddles is one of the most important tasks in theor. study of chem. reaction. Although automated search has been established either by starting from a local min. (MIN) or by connecting two MINs, there is no systematic method which can locate TSs of A + B → X (+ Y) type reactions starting from sepd. reactants. We propose such an approach for the first time; it was demonstrated to work very well in the SN2, Diels-Alder, and Wittig reactions. (c) 2010 American Institute of Physics.
- 26Maeda, S.; Morokuma, K. Finding Reaction Pathways of Type A+B→X: Toward Systematic Prediction of Reaction Mechanisms. J. Chem. Theory Comput. 2011, 7, 2335– 2345, DOI: 10.1021/ct200290m26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXosVCktro%253D&md5=85e666d25ec4858a5150bae96893f52aFinding Reaction Pathways of Type A + B → X: Toward Systematic Prediction of Reaction MechanismsMaeda, Satoshi; Morokuma, KeijiJournal of Chemical Theory and Computation (2011), 7 (8), 2335-2345CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)In these five decades, many useful tools have been developed for exploring quantum chem. potential energy surfaces. The success in theor. studies of chem. reaction mechanisms has been greatly supported by these tools. However, systematic prediction of reaction mechanisms starting only from given reactants and catalysts is still very difficult. Toward this goal, we describe the artificial force induced reaction (AFIR) method for automatically finding reaction paths of type A + B → X (+ Y). By imposing an artificial force to given reactants and catalysts, the method can find the reactive sites very efficiently. Further pressing by the artificial force provides approx. transition states and product structures, which can be easily reoptimized to the corresponding true ones. This procedure can be executed very efficiently just by minimizing a single function called the AFIR function. All important reaction paths can be found by repeating this cycle starting from many initial orientations. We also discuss perspectives of automated reaction path search methods toward the above goal.
- 27Maeda, S.; Taketsugu, T.; Morokuma, K. Exploring Transition State Structures for Intramolecular Pathways by the Artificial Force Induced Reaction Method. J. Comput. Chem. 2014, 35, 166– 173, DOI: 10.1002/jcc.2348127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslaqs77J&md5=18ee5becec9b21d0bdcef4d37b50a48dExploring transition state structures for intramolecular pathways by the artificial force induced reaction methodMaeda, Satoshi; Taketsugu, Tetsuya; Morokuma, KeijiJournal of Computational Chemistry (2014), 35 (2), 166-173CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Finding all required transition state (TS) structures is an important but hard task in theor. study of complex reaction mechanisms. An efficient automated TS search method, artificial force induced reaction (AFIR), was extended to intramol. reactions. The AFIR method was developed for intermol. associative pathways between two or more reactants. Although it also was applied to intramol. reactions by dividing mols. manually into fragments, the fragmentation scheme was not automated. The authors propose an automated fragmentation scheme. Using this fragmentation scheme and the AFIR method, a fully automated search algorithm for intramol. pathways is introduced. This version for intramol. reactions is called single-component AFIR (SC-AFIR), to distinguish it from multicomponent AFIR for intermol. reactions. SC-AFIR was tested with two reactions, the Claisen rearrangement and the first step of cobalt-catalyzed hydroformylation, and successfully located all important pathways reported in the literature. © 2013 Wiley Periodicals, Inc.
- 28Maeda, S.; Harabuchi, Y.; Takagi, M.; Taketsugu, T.; Morokuma, K. Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy Surfaces. Chem. Rec. 2016, 16, 2232– 2248, DOI: 10.1002/tcr.20160004328https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XptV2iurg%253D&md5=fb8514d68f9fefc53f4d5f9ad8e19e06Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy SurfacesMaeda, Satoshi; Harabuchi, Yu; Takagi, Makito; Taketsugu, Tetsuya; Morokuma, KeijiChemical Record (2016), 16 (5), 2232-2248CODEN: CRHEAK; ISSN:1528-0691. (Wiley-VCH Verlag GmbH & Co. KGaA)In this account, a tech. overview of the artificial force induced reaction (AFIR) method is presented. The AFIR method is one of the automated reaction-path search methods developed by the authors, and has been applied extensively to a variety of chem. reactions, such as organocatalysis, organometallic catalysis, and photoreactions. There are two modes in the AFIR method, i.e., a multicomponent mode and a single-component mode. The former has been applied to bimol. and multicomponent reactions and the latter to unimol. isomerization and dissocn. reactions. Five numerical examples are presented for an Aldol reaction, a Claisen rearrangement, a Co-catalyzed hydroformylation, a fullerene structure search, and a nonradiative decay path search in an electronically excited naphthalene mol. Finally, possible applications of the AFIR method are discussed.
- 29Yoshimura, T.; Maeda, S.; Taketsugu, T.; Sawamura, M.; Morokuma, K.; Mori, S. Exploring the Full Catalytic Cycle of Rhodium(I)–BINAP-Catalysed Isomerisation of Allylic Amines: A Graph Theory Approach for Path Optimisation. Chem. Sci. 2017, 8, 4475– 4488, DOI: 10.1039/C7SC00401J29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntlWgt7s%253D&md5=c2ab51df0053f782bc9e9f5323ec2358Exploring the full catalytic cycle of rhodium(I)-BINAP-catalysed isomerisation of allylic amines: a graph theory approach for path optimisationYoshimura, Takayoshi; Maeda, Satoshi; Taketsugu, Tetsuya; Sawamura, Masaya; Morokuma, Keiji; Mori, SeijiChemical Science (2017), 8 (6), 4475-4488CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)We explored the reaction mechanism of the cationic rhodium(I)-BINAP complex catalyzed isomerization of allylic amines using the artificial force induced reaction method with the global reaction route mapping strategy, which enabled us to search for various reaction paths without assumption of transition states. The entire reaction network was reproduced in the form of a graph, and reasonable paths were selected from the complicated network using Prim's algorithm. As a result, a new dissociative reaction mechanism was proposed. Our comprehensive reaction path search provided rationales for the E/Z and S/R selectivities of the stereoselective reaction.
- 30Puripat, M.; Ramozzi, R.; Hatanaka, M.; Parasuk, W.; Parasuk, V.; Morokuma, K. The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent Reaction. J. Org. Chem. 2015, 80, 6959– 6967, DOI: 10.1021/acs.joc.5b0040730https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVans7nM&md5=7f6185df4c8e5c3802f013bc36a694c7The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent ReactionPuripat, Maneeporn; Ramozzi, Romain; Hatanaka, Miho; Parasuk, Waraporn; Parasuk, Vudhichai; Morokuma, KeijiJournal of Organic Chemistry (2015), 80 (14), 6959-6967CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)The recently developed artificial force induced reaction (AFIR) method was applied to search systematically all possible multicomponent pathways for the Biginelli reaction mechanism. The most favorable pathway starts with the condensation of the urea and benzaldehyde, followed by the addn. of Et acetoacetate. Remarkably, a second urea mol. catalyzes nearly every step of the reaction. Thus, the Biginelli reaction is a urea-catalyzed multicomponent reaction. The reaction mechanism was found to be identical in both protic and aprotic solvents.
- 31Saitta, A. M.; Saija, F. Miller Experiments in Atomistic Computer Simulations. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 13768– 13773, DOI: 10.1073/pnas.140289411131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFSju7nN&md5=711514af5c0a3a8d6d0a226d29be2d8bMiller experiments in atomistic computer simulationsSaitta, Antonino Marco; Saija, FranzProceedings of the National Academy of Sciences of the United States of America (2014), 111 (38), 13768-13773CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The celebrated Miller expts. reported on the spontaneous formation of amino acids from a mixt. of simple mols. reacting under an elec. discharge, giving birth to the research field of prebiotic chem. However, the chem. reactions involved in those expts. have never been studied at the at. level. Here the authors report on, to the authors' knowledge, the first ab initio computer simulations of Miller-like expts. in the condensed phase. The authors' study, based on the recent method of treatment of aq. systems under elec. fields and on metadynamics anal. of chem. reactions, shows that glycine spontaneously forms from mixts. of simple mols. once an elec. field is switched on and identifies formic acid and formamide as key intermediate products of the early steps of the Miller reactions, and the crucible of formation of complex biol. mols.
- 32Wang, L.-P.; Titov, A.; McGibbon, R.; Liu, F.; Pande, V. S.; Martínez, T. J. Discovering Chemistry with an Ab Initio Nanoreactor. Nat. Chem. 2014, 6, 1044– 1048, DOI: 10.1038/nchem.209932https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVGitbnI&md5=201fe998c04f0c9b9a7aa6ebf329a2c5Discovering chemistry with an ab initio nanoreactorWang, Lee-Ping; Titov, Alexey; McGibbon, Robert; Liu, Fang; Pande, Vijay S.; Martinez, Todd J.Nature Chemistry (2014), 6 (12), 1044-1048CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)Chem. understanding is driven by the exptl. discovery of new compds. and reactivity, and is supported by theory and computation that provide detailed phys. insight. Although theor. and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodol. and computational advances harken the advent of their principal role in discovery. Here, we report the development and application of the ab initio nanoreactor-a highly accelerated first-principles mol. dynamics simulation of chem. reactions that discovers new mols. and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor, we show new pathways for glycine synthesis from primitive compds. proposed to exist on the early Earth, which provide new insight into the classic Urey-Miller expt. These results highlight the emergence of theor. and computational chem. as a tool for discovery, in addn. to its traditional role of interpreting exptl. findings.
- 33Wang, L.-P.; McGibbon, R. T.; Pande, V. S.; Martinez, T. J. Automated Discovery and Refinement of Reactive Molecular Dynamics Pathways. J. Chem. Theory Comput. 2016, 12, 638– 649, DOI: 10.1021/acs.jctc.5b0083033https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVGku7nL&md5=6a731baa0767e0105247b156289fe8baAutomated Discovery and Refinement of Reactive Molecular Dynamics PathwaysWang, Lee-Ping; McGibbon, Robert T.; Pande, Vijay S.; Martinez, Todd J.Journal of Chemical Theory and Computation (2016), 12 (2), 638-649CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We describe a flexible and broadly applicable energy refinement method, "nebterpolation," for identifying and characterizing the reaction events in a mol. dynamics (MD) simulation. The new method is applicable to ab initio simulations with hundreds of atoms contg. complex and multimol. reaction events. A key aspect of nebterpolation is smoothing of the reactive MD trajectory in internal coordinates to initiate the search for the reaction path on the potential energy surface. We apply nebterpolation to analyze the reaction events in an ab initio nanoreactor simulation that discovers new mols. and mechanisms, including a C-C coupling pathway for glycolaldehyde synthesis. We find that the new method, which incorporates information from the MD trajectory that connects reactants with products, produces a dramatically distinct set of min. energy paths compared to existing approaches that start from information for the reaction end points alone. The energy refinement method described here represents a key component of an emerging simulation paradigm where mol. dynamics simulations are applied to discover the possible reaction mechanisms.
- 35van Duin, A. C. T.; Dasgupta, S.; Lorant, F.; Goddard, W. A. ReaxFF: A Reactive Force Field for Hydrocarbons. J. Phys. Chem. A 2001, 105, 9396– 9409, DOI: 10.1021/jp004368u35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFChu78%253D&md5=ea59efc08d5e135745df988f2006a7fdReaxFF: A Reactive Force Field for Hydrocarbonsvan Duin, Adri C. T.; Dasgupta, Siddharth; Lorant, Francois; Goddard, William A., IIIJournal of Physical Chemistry A (2001), 105 (41), 9396-9409CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)To make practical the mol. dynamics simulation of large scale reactive chem. systems (1000 s of atoms), the authors developed ReaxFF, a force field for reactive systems. ReaxFF uses a general relation between bond distance and bond order on one hand and between bond order and bond energy however, that leads to proper dissocn. of bonds to sepd. atoms. Other valence terms present in the force field (angle and torsion) are defined in terms of the same bond orders so that all these terms go to zero smoothly as bonds break. In addn., ReaxFF has Coulomb and Morse (van der Waals) potentials to describe nonbond interactions between all atoms (no exclusions). These nonbond interactions are shielded at short range so that the Coulomb and van der Waals interactions become const. as Rij → 0. The authors report here the ReaxFF for hydrocarbons. The parameters were derived from quantum chem. calcns. on bond dissocn. and reactions of small mols. plus heat of formation and geometry data for a no. of stable hydrocarbon compds. The ReaxFF provides a good description of these data. Generally, the results are of an accuracy similar or better than PM3, while ReaxFF is ∼100 times faster. In turn, the PM3 is ∼100 times faster than the QC calcns. Thus, with ReaxFF the authors hope to be able to study complex reactions in hydrocarbons.
- 36Döntgen, M.; Przybylski-Freund, M.-D.; Kröger, L. C.; Kopp, W. A.; Ismail, A. E.; Leonhard, K. Automated Discovery of Reaction Pathways, Rate Constants, and Transition States Using Reactive Molecular Dynamics Simulations. J. Chem. Theory Comput. 2015, 11, 2517– 2524, DOI: 10.1021/acs.jctc.5b0020136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28vjt1Gjtg%253D%253D&md5=7f936903e2258f886ccce3fc8fef0996Automated discovery of reaction pathways, rate constants, and transition states using reactive molecular dynamics simulationsDontgen Malte; Przybylski-Freund Marie-Dominique; Kroger Leif C; Kopp Wassja A; Ismail Ahmed E; Leonhard KaiJournal of chemical theory and computation (2015), 11 (6), 2517-24 ISSN:.We provide a methodology for deducing quantitative reaction models from reactive molecular dynamics simulations by identifying, quantifying, and evaluating elementary reactions of classical trajectories. Simulations of the inception stage of methane oxidation are used to demonstrate our methodology. The agreement of pathways and rates with available literature data reveals the potential of reactive molecular dynamics studies for developing quantitative reaction models.
- 37Fischer, S.; Karplus, M. Conjugate Peak Refinement: An Algorithm for Finding Reaction Paths and Accurate Transition States in Systems with Many Degrees of Freedom. Chem. Phys. Lett. 1992, 194, 252– 261, DOI: 10.1016/0009-2614(92)85543-J37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XltFSqtrk%253D&md5=938aae7d35f6942adbd76bf19c19cf9dConjugate peak refinement: an algorithm for finding reaction paths and accurate transition states in systems with many degrees of freedomFischer, Stefan; Karplus, MartinChemical Physics Letters (1992), 194 (3), 252-61CODEN: CHPLBC; ISSN:0009-2614.An algorithm is presented for detg. multidimensional reaction coordinates between two known conformers. Only the energy function and its gradient are required. The resulting paths follow the adiabatic energy valleys and have energy max. that are true saddle points, which can be multiple along each path. The method is suitable for the study of complex isomerization reactions, including allosteric transitions in proteins and more general conformational changes of macromols.
- 38Florián, J.; Goodman, M. F.; Warshel, A. Computer Simulation of the Chemical Catalysis of DNA Polymerases: Discriminating between Alternative Nucleotide Insertion Mechanisms for T7 DNA Polymerase. J. Am. Chem. Soc. 2003, 125, 8163– 8177, DOI: 10.1021/ja028997o38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXksFWgsbY%253D&md5=98029baf5458f072872a0746ea5ab990Computer simulation of the chemical catalysis of DNA polymerases: Discriminating between alternative nucleotide insertion mechanisms for T7 DNA polymeraseFlorian, Jan; Goodman, Myron F.; Warshel, AriehJournal of the American Chemical Society (2003), 125 (27), 8163-8177CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Understanding the chem. step in the catalytic reaction of DNA polymerases is essential for elucidating the mol. basis of the fidelity of DNA replication. The present work evaluates the free energy surface for the nucleotide transfer reaction of T7 polymerase by free energy perturbation/empirical valence bond (FEP/EVB) calcns. A key aspect of the enzyme simulation is a comparison of enzymic free energy profiles with the corresponding ref. reactions in water using the same computational methodol., thereby enabling a quant. est. for the free energy of the nucleotide insertion reaction. The reaction is driven by the FEP/EVB methodol. between valence bond structures representing the reactant, pentacovalent intermediate, and the product states. This pathway corresponds to three microscopic chem. steps, deprotonation of the attacking group, a nucleophilic attack on the Pα atom of the dNTP substrate, and departure of the leaving group. Three different mechanisms for the first microscopic step, the generation of the RO- nucleophile from the 3'-OH hydroxyl of the primer, are examd.: (i) proton transfer to the bulk solvent, (ii) proton transfer to one of the ionic oxygens of the Pα phosphate group, and (iii) proton transfer to the ionized Asp 654 residue. The most favorable reaction mechanism in T7 pol is predicted to involve the proton transfer to Asp 654. This finding sheds light on the long standing issue of the actual role of conserved aspartates. The structural preorganization that helps to catalyze the reaction is also considered and analyzed. The overall calcd. mechanism consists of three subsequent steps with a similar activation free energy of about 12 kcal/mol. The similarity of the activation barriers of the three microscopic chem. steps indicates that the T7 polymerase may select against the incorrect dNTP substrate by raising any of these barriers. The relative height of these barriers comparing right and wrong dNTP substrates should therefore be a primary focus of future computational studies of the fidelity of DNA polymerases.
- 39Garcia-Viloca, M.; Gao, J.; Karplus, M.; Truhlar, D. G. How Enzymes Work: Analysis by Modern Rate Theory and Computer Simulations. Science 2004, 303, 186– 195, DOI: 10.1126/science.108817239https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhtlGhug%253D%253D&md5=35766752530af526c8bdc99774a8e9daHow enzymes work: Analysis by modern rate theory and computer simulationsGarcia-Viloca, Mireia; Gao, Jiali; Karplus, Martin; Truhlar, Donald G.Science (Washington, DC, United States) (2004), 303 (5655), 186-195CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review and discussion. Advances in transition state theory and computer simulations are providing new insights into the sources of enzyme catalysis. Both the lowering of the activation free energy and changes in the generalized transmission coeff. (recrossing of the transition state, tunneling, and nonequil. contributions) can play a role. A framework for understanding these effects is presented, and the contributions of the different factors, as illustrated by specific enzymes, are identified and quantified by computer simulations. The resulting understanding of enzyme catalysis is used to comment on alternative proposals of how enzymes work.
- 40Imhof, P.; Fischer, S.; Smith, J. C. Catalytic Mechanism of DNA Backbone Cleavage by the Restriction Enzyme EcoRV: A Quantum Mechanical/Molecular Mechanical Analysis. Biochemistry 2009, 48, 9061– 9075, DOI: 10.1021/bi900585m40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtV2mtbvP&md5=88ce54a5f9131bc8ad11b1dbd07f8e6eCatalytic Mechanism of DNA Backbone Cleavage by the Restriction Enzyme EcoRV: A Quantum Mechanical/Molecular Mechanical AnalysisImhof, Petra; Fischer, Stefan; Smith, Jeremy C.Biochemistry (2009), 48 (38), 9061-9075CODEN: BICHAW; ISSN:0006-2960. (American Chemical Society)Endonucleases, such as the restriction enzyme EcoRV, cleave the DNA backbone at a specific recognition sequence. We have investigated the catalytic mechanism of backbone phosphodiester hydrolysis by the restriction enzyme EcoRV by means of hybrid quantum mech./mol. mech. calcns. An exhaustive computation of different reaction pathways is performed, thus generating a network of pathways. Comparison of the computed (AM1d/MM) enzymic reaction pathways with an analogous mechanism for small-mol. model systems [AM1/d and B3LYP/6-31++G(d,p)] reveals that the transition barriers for associative hydrolysis, which is more probable in the model systems, are not lowered by the enzyme. Instead, a reaction mechanism which has mostly dissociative character is more likely. The protein environment is tuned to significantly electrostatically stabilize the transition state structures. The direct catalytic impact of essential residues is detd. The magnesium metal ion activates a water mol., thus facilitating protonation of the leaving group. A redn. of the coordination no. of the magnesium metal ion from six to four upon the positioning of the attacking water mol. explains why larger metal ions, such as calcium, are not catalytically active. The nucleophile is generated by the transfer of a proton from the attacking water mol. to a carboxylic oxygen atom of aspartate 90. The catalytic effect of lysine 92 involves proper positioning of the scissile phosphate group and, more importantly, stabilization of the metaphosphate intermediate in an orientation optimal for attack of the nucleophile.
- 43Senn, H. M.; Thiel, W. QM/MM Methods for Biological Systems. Top. Curr. Chem. 2007, 268, 173– 290, DOI: 10.1007/128_2006_08443https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjvVOlt7c%253D&md5=bf5f07823db75b3e05018ed47b70d2c1QM/MM methods for biological systemsSenn, Hans Martin; Thiel, WalterTopics in Current Chemistry (2007), 268 (Atomistic Approaches in Modern Biology), 173-290CODEN: TPCCAQ; ISSN:0340-1022. (Springer GmbH)A review. Thirty years after the seminal contribution by Warshel and Levitt, we review the state of the art of combined quantum-mechanics/mol.-mechanics (QM/MM) methods, with a focus on biomol. systems. We provide a detailed overview of the methodol. of QM/MM calcns. and their use within optimization and simulation schemes. A tabular survey of recent applications, mostly to enzymic reactions, is given.
- 44Senn, H. M.; Thiel, W. QM/MM Studies of Enzymes. Curr. Opin. Chem. Biol. 2007, 11, 182– 187, DOI: 10.1016/j.cbpa.2007.01.68444https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjvFegurw%253D&md5=361cc5b164e23e5a71dac6f4bbf7d673QM/MM studies of enzymesSenn, Hans Martin; Thiel, WalterCurrent Opinion in Chemical Biology (2007), 11 (2), 182-187CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)A review. Combined quantum-mechanics/mol.-mechanics (QM/MM) methods are making rapid progress both methodol. and with respect to their range of application. Mechanistic studies on enzymes, including contributions toward the understanding of enzyme catalysis, continue to be a major target. They are joined by calcns. of pKa values, redox properties, ground- and excited-state spectroscopic parameters, and excited-state dynamics. Methodol. advances include improved QM/MM schemes, in particular new approaches for an effective treatment of the QM-MM electrostatic interactions, and the incorporation of new efficient and accurate QM methods in QM/MM schemes.
- 45Senn, H. M.; Thiel, W. QM/MM Methods for Biomolecular Systems. Angew. Chem., Int. Ed. 2009, 48, 1198– 1229, DOI: 10.1002/anie.20080201945https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXitFOqs7g%253D&md5=c51da58b0525651c71f9c393a79023beQM/MM methods for biomolecular systemsSenn, Hans Martin; Thiel, WalterAngewandte Chemie, International Edition (2009), 48 (7), 1198-1229CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Combined quantum-mechanics/mol.-mechanics (QM/MM) approaches have become the method of choice for modeling reactions in biomol. systems. Quantum-mech. (QM) methods are required for describing chem. reactions and other electronic processes, such as charge transfer or electronic excitation. However, QM methods are restricted to systems of up to a few hundred atoms. However, the size and conformational complexity of biopolymers calls for methods capable of treating up to several 100,000 atoms and allowing for simulations over time scales of tens of nanoseconds. This is achieved by highly efficient, force-field-based mol. mechanics (MM) methods. Thus to model large biomols. the logical approach is to combine the two techniques and, to use a QM method for the chem. active region (e.g., substrates and co-factors in an enzymic reaction) and an MM treatment for the surroundings (e.g., protein and solvent). The resulting schemes are commonly referred to as combined or hybrid QM/MM methods. They enable the modeling of reactive biomol. systems at a reasonable computational effort while providing the necessary accuracy.
- 46Huber, T.; Torda, A. E.; van Gunsteren, W. F. Local Elevation: A Method for Improving the Searching Properties of Molecular Dynamics Simulation. J. Comput.-Aided Mol. Des. 1994, 8, 695– 708, DOI: 10.1007/BF0012401646https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXjtVOnsrw%253D&md5=8d352c5753f9870081d4851ff12e58cdLocal elevation: a method for improving the searching properties of molecular dynamics simulationHuber, Thomas; Torda, Andrew E.; van Gunsteren, Wilfred F.Journal of Computer-Aided Molecular Design (1994), 8 (6), 695-708CODEN: JCADEQ; ISSN:0920-654X. (ESCOM)The concept of memory has been introduced into a mol. dynamics algorithm. This was done so as to persuade a mol. system to visit new areas of conformational space rather than be confined to a small no. of low-energy regions. The method is demonstrated on a simple model system and the 11-residue cyclic peptide cyclosporin A. For comparison, calcns. were also performed using simulated temp. annealing and a potential energy annealing scheme. Although the method can only be applied to systems with a small no. of degrees of freedom, it offers the chance to generate a multitude of different low-energy structures, where other methods only give a single one or few. This is clearly important in problems such as drug design, where one is interested in the conformational spread of a system.
- 47Laio, A.; Parrinello, M. Escaping Free-Energy Minima. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 12562– 12566, DOI: 10.1073/pnas.20242739947https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XnvFGiurc%253D&md5=48d5bc7436f3ef9d78369671e70fa608Escaping free-energy minimaLaio, Alessandro; Parrinello, MicheleProceedings of the National Academy of Sciences of the United States of America (2002), 99 (20), 12562-12566CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)We introduce a powerful method for exploring the properties of the multidimensional free energy surfaces (FESs) of complex many-body systems by means of coarse-grained non-Markovian dynamics in the space defined by a few collective coordinates. A characteristic feature of these dynamics is the presence of a history-dependent potential term that, in time, fills the min. in the FES, allowing the efficient exploration and accurate detn. of the FES as a function of the collective coordinates. We demonstrate the usefulness of this approach in the case of the dissocn. of a NaCl mol. in water and in the study of the conformational changes of a dialanine in soln.
- 48Christen, M.; van Gunsteren, W. F. On Searching in, Sampling of, and Dynamically Moving through Conformational Space of Biomolecular Systems: A Review. J. Comput. Chem. 2008, 29, 157– 166, DOI: 10.1002/jcc.2072548https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2sjktVOitQ%253D%253D&md5=c508200635d58b25f5ee678a9c016f87On searching in, sampling of, and dynamically moving through conformational space of biomolecular systems: A reviewChristen Markus; van Gunsteren Wilfred FJournal of computational chemistry (2008), 29 (2), 157-66 ISSN:0192-8651.Methods to search for low-energy conformations, to generate a Boltzmann-weighted ensemble of configurations, or to generate classical-dynamical trajectories for molecular systems in the condensed liquid phase are briefly reviewed with an eye to application to biomolecular systems. After having chosen the degrees of freedom and method to generate molecular configurations, the efficiency of the search or sampling can be enhanced in various ways: (i) efficient calculation of the energy function and forces, (ii) application of a plethora of search enhancement techniques, (iii) use of a biasing potential energy term, and (iv) guiding the sampling using a reaction or transition pathway. The overview of the available methods should help the reader to choose the combination that is most suitable for the biomolecular system, degrees of freedom, interaction function, and molecular or thermodynamic properties of interest.
- 49Bernardi, R. C.; Melo, M. C. R.; Schulten, K. Enhanced Sampling Techniques in Molecular Dynamics Simulations of Biological Systems. Biochim. Biophys. Acta, Gen. Subj. 2015, 1850, 872– 877, DOI: 10.1016/j.bbagen.2014.10.01949https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVanurbN&md5=44e3ac1aa042c35ee08aa86a6a63e78eEnhanced sampling techniques in molecular dynamics simulations of biological systemsBernardi, Rafael C.; Melo, Marcelo C. R.; Schulten, KlausBiochimica et Biophysica Acta, General Subjects (2015), 1850 (5), 872-877CODEN: BBGSB3; ISSN:0304-4165. (Elsevier B.V.)A review. Mol. dynamics has emerged as an important research methodol. covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local min. sepd. by high-energy barriers, which govern the biomol. motion. In the past few decades methods have been developed that address the sampling problem, such as replica-exchange mol. dynamics, metadynamics and simulated annealing. Here the authors present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Enhanced sampling methods have been employed for a broad range of biol. systems and the choice of a suitable method is connected to biol. and phys. characteristics of the system, in particular system size. While metadynamics and replica-exchange mol. dynamics are the most adopted sampling methods to study biomol. dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromol. complexes. Mol. dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biol. function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of mol. dynamics.
- 50Shim, J.; MacKerell, A. D., Jr. Computational Ligand-Based Rational Design: Role of Conformational Sampling and Force Fields in Model Development. MedChemComm 2011, 2, 356– 370, DOI: 10.1039/c1md00044f50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1Kht7c%253D&md5=70d822d1ca2faa484f723fb109597b77Computational ligand-based rational design: role of conformational sampling and force fields in model developmentShim, Jihyun; MacKerell, Alexander D., Jr.MedChemComm (2011), 2 (5), 356-370CODEN: MCCEAY; ISSN:2040-2503. (Royal Society of Chemistry)A review. A significant no. of drug discovery efforts are based on natural products or high throughput screens from which compds. showing potential therapeutic effects are identified without knowledge of the target mol. or its 3D structure. In such cases computational ligand-based drug design (LBDD) can accelerate the drug discovery processes. LBDD is a general approach to elucidate the relationship of a compd.'s structure and physicochem. attributes to its biol. activity. The resulting structure-activity relationship (SAR) may then act as the basis for the prediction of compds. with improved biol. attributes. LBDD methods range from pharmacophore models identifying essential features of ligands responsible for their activity, quant. structure-activity relationships (QSAR) yielding quant. ests. of activities based on physiochem. properties, and to similarity searching, which explores compds. with similar properties as well as various combinations of the above. A no. of recent LBDD approaches involve the use of multiple conformations of the ligands being studied. One of the basic components to generate multiple conformations in LBDD is mol. mechanics (MM), which apply an empirical energy function to relate conformation to energies and forces. The collection of conformations for ligands is then combined with functional data using methods ranging from regression anal. to neural networks, from which the SAR is detd. Accordingly, for effective application of LBDD for SAR detns. it is important that the compds. be accurately modelled such that the appropriate range of conformations accessible to the ligands is identified. Such accurate modeling is largely based on use of the appropriate empirical force field for the mols. being investigated and the approaches used to generate the conformations. The present chapter includes a brief overview of currently used SAR methods in LBDD followed by a more detailed presentation of issues and limitations assocd. with empirical energy functions and conformational sampling methods.
- 52De Vivo, M.; Masetti, M.; Bottegoni, G.; Cavalli, A. Role of Molecular Dynamics and Related Methods in Drug Discovery. J. Med. Chem. 2016, 59, 4035– 4061, DOI: 10.1021/acs.jmedchem.5b0168452https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlWksLs%253D&md5=b3d8a4fb5705a3555c2bb2a962420396Role of Molecular Dynamics and Related Methods in Drug DiscoveryDe Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, AndreaJournal of Medicinal Chemistry (2016), 59 (9), 4035-4061CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society)Mol. dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate est. of the thermodn. and kinetics assocd. with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theor. background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water mols. in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates.
- 54Wilson, S. R.; Cui, W.; Moskowitz, J. W.; Schmidt, K. E. Applications of Simulated Annealing to the Conformational Analysis of Flexible Molecules. J. Comput. Chem. 1991, 12, 342– 349, DOI: 10.1002/jcc.54012030754https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3MXitVKhsLw%253D&md5=7ca487c05c358c760a76eed13145b5deApplications of simulated annealing to the conformational analysis of flexible moleculesWilson, Stephen R.; Cui, Weili; Moskowitz, Jules W.; Schmidt, Kevin E.Journal of Computational Chemistry (1991), 12 (3), 342-9CODEN: JCCHDD; ISSN:0192-8651.A soln. to the global min. problem which uses the simulated annealing algorithm of Kirkpatrick is described. This method is a Metropolis (e-ΔE/kT) Monte Carlo sampling of conformation space with simultaneous constraint of the search by lowering the temp. T so that the search converges on the global min. The Anneal-Conformer program has been extensively tested with peptides and org. mols. using either the Amber or MM2 force fields. A history file of the simulated annealing process allows reconstruction of the random walk in conformation space for subsequent examn. Thus plots of distance and dihedral angle changes during the search for the global min. can be examd. to deduce mol. shape and flexibility. A sep. program Conf-Gen reads the history file and exts. all low energy conformations visited during the run.
- 55Sperandio, O.; Souaille, M.; Delfaud, F.; Miteva, M. A.; Villoutreix, B. O. MED-3DMC: A New Tool to Generate 3D Conformation Ensembles of Small Molecules with a Monte Carlo Sampling of the Conformational Space. Eur. J. Med. Chem. 2009, 44, 1405– 1409, DOI: 10.1016/j.ejmech.2008.09.05255https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjtVSjtLw%253D&md5=bc3b0f5ea5b23da6eec7048f39081448MED-3DMC: A new tool to generate 3D conformation ensembles of small molecules with a Monte Carlo sampling of the conformational spaceSperandio, Olivier; Souaille, Marc; Delfaud, Francois; Miteva, Maria A.; Villoutreix, Bruno O.European Journal of Medicinal Chemistry (2009), 44 (4), 1405-1409CODEN: EJMCA5; ISSN:0223-5234. (Elsevier Masson SAS)Obtaining an efficient sampling of the low to medium energy regions of a ligand conformational space is of primary importance for getting insight into relevant binding modes of drug candidates, or for the screening of rigid mol. entities on the basis of a predefined pharmacophore or for rigid body docking. Here, we report the development of a new computer tool that samples the conformational space by using the Metropolis Monte Carlo algorithm combined with the MMFF94 van der Waals energy term. The performances of the program have been assessed on 86 drug-like mols. that resulted from an ADME/tox profiling applied on cocrystalized small mols. and were compared with the program Omega on the same dataset. Our program has also been assessed on the 85 mols. of the Astex diverse set. Both test sets show convincing performance of our program at sampling the conformational space.
- 57Shang, C.; Liu, Z.-P. Stochastic Surface Walking Method for Structure Prediction and Pathway Searching. J. Chem. Theory Comput. 2013, 9, 1838– 1845, DOI: 10.1021/ct301010b57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOlt7c%253D&md5=ff2585b886e8cc63d4443934f5317048Stochastic Surface Walking Method for Structure Prediction and Pathway SearchingShang, Cheng; Liu, Zhi-PanJournal of Chemical Theory and Computation (2013), 9 (3), 1838-1845CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We propose an unbiased general-purpose potential energy surface (PES) searching method for both the structure and the pathway prediction of a complex system. The method is based on the idea of bias-potential-driven dynamics and Metropolis Monte Carlo. A central feature of the method is able to perturb smoothly a structural configuration toward a new configuration and simultaneously has the ability to surmount the high barrier in the path. We apply the method for locating the global min. (GM) of short-ranged Morse clusters up to 103 atoms starting from a random structure without using extra information from the system. In addn. to GM searching, the method can identify the pathways for chem. reactions with large dimensionality, as demonstrated in a nanohelix transformation contg. 222 degrees of freedoms.
- 58Zhang, X.-J.; Shang, C.; Liu, Z.-P. From Atoms to Fullerene: Stochastic Surface Walking Solution for Automated Structure Prediction of Complex Material. J. Chem. Theory Comput. 2013, 9, 3252– 3260, DOI: 10.1021/ct400238j58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXosVegsr0%253D&md5=0e94b080ff99b33134c703b183357f15From Atoms to Fullerene: Stochastic Surface Walking Solution for Automated Structure Prediction of Complex MaterialZhang, Xiao-Jie; Shang, Cheng; Liu, Zhi-PanJournal of Chemical Theory and Computation (2013), 9 (7), 3252-3260CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)It is of general concern whether the automated structure prediction of unknown material without recourse to any knowledge from expt. is ever possible considering the daunting complexity of potential energy surface (PES) of material. Here we demonstrate that the stochastic surface walking (SSW) method can be a general and promising soln. to this ultimate goal, which is applied to assemble carbon fullerenes contg. up to 100 atoms (including 60, 70, 76, 78, 80, 84, 90, 96, and 100 atoms) from randomly distributed atoms, a long-standing challenge in global optimization. Combining the SSW method with a parallel replica exchange algorithm, we can locate the global min. (GM) of these large fullerenes efficiently without being trapped in numerous energy-nearly degenerate isomers. Detailed analyses on the SSW trajectories allow us to rationalize how and why the SSW method is able to explore the highly complex PES, which highlights the abilities of SSW method for surmounting the high barrier and the preference of SSW trajectories to the low energy pathways. The work demonstrates that the parallel SSW method is a practical tool for predicting unknown materials.
- 59Shang, C.; Zhang, X.-J.; Liu, Z.-P. Stochastic Surface Walking Method for Crystal Structure and Phase Transition Pathway Prediction. Phys. Chem. Chem. Phys. 2014, 16, 17845– 17856, DOI: 10.1039/C4CP01485E59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFyms7jE&md5=c5dc152fa492d8978d79bbcf35313753Stochastic surface walking method for crystal structure and phase transition pathway predictionShang, Cheng; Zhang, Xiao-Jie; Liu, Zhi-PanPhysical Chemistry Chemical Physics (2014), 16 (33), 17845-17856CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The detn. of crystal structures and the solid-to-solid phase transition mechanisms are two important and related subjects in material science. Here we develop an unbiased general-purpose potential energy surface (PES) searching method, namely, SSW-crystal method, for prediction of both the crystal structure and the crystal phase transition pathway. The SSW-crystal method features with stochastic surface walking (SSW) via repeated small structural perturbation by taking into account the second deriv. information on both the lattice and the atom degrees of freedom. The SSW-crystal method is capable of overcoming the high barrier of phase transition and identifying the desirable phase transition reaction coordinates. By applying the SSW-crystal method to a set of examples, including SiO2 crystal up to 162 atoms per cell, Lennard-Jones model crystals up to 256 atoms, ternary SrTiO3 crystal of 50 atoms and the rutile-to-anatase TiO2 phase transition, we show that the SSW-crystal method can efficiently locate the global min. (GM) from random initial structures without a priori knowledge of the system, and also allows for exhaustive sampling of the phase transition pathways, from which the lowest energy pathway can be obtained.
- 60Zhang, X.-J.; Liu, Z.-P. Reaction Sampling and Reactivity Prediction Using the Stochastic Surface Walking Method. Phys. Chem. Chem. Phys. 2015, 17, 2757– 2769, DOI: 10.1039/C4CP04456H60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVSgur3F&md5=c5ac6082903ea35d005a1e00ab73febeReaction sampling and reactivity prediction using the stochastic surface walking methodZhang, Xiao-Jie; Liu, Zhi-PanPhysical Chemistry Chemical Physics (2015), 17 (4), 2757-2769CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The prediction of chem. reactivity and thus the design of new reaction systems are the key challenges in chem. Here, we develop an unbiased general-purpose reaction sampling method, the stochastic surface walking based reaction sampling (SSW-RS) method, and show that the new method is a promising soln. for reactivity prediction of complex reaction systems. The SSW-RS method is capable of sampling both the configuration space of the reactant and the reaction space of pathways, owing to the combination of two recently developed theor. methods, namely, the stochastic surface walking (SSW) method for potential energy surface (PES) exploration and the double-ended surface walking (DESW) method for building pathways. By integrating with first principles calcns., we show that the SSW-RS method can be applied to investigate the kinetics of complex org. reactions featuring many possible reaction channels and complex hydrogen-bonding networks, as demonstrated here using two examples, epoxypropane hydrolysis in aq. soln. and β-D-glucopyranose decompn. Our results show that simultaneous sampling of the soft hydrogen-bonding conformations and the chem. reactions involving hard bond making/breaking can be achieved in the SSW-RS simulation, and the mechanism and kinetics can be predicted without a priori information on the system. Unexpected new chem. for these reactions is revealed and discussed. In particular, despite many possible pathways for β-D-glucopyranose decompn., the SSW-RS shows that only β-D-glucose and levoglucosan are kinetically preferred direct products and the 5- or 7-member ring products should be secondary products derived from β-D-glucose or levoglucosan. As a general tool for reactivity prediction, the SSW-RS opens a new route for the design of rational reactions.
- 61Vázquez, S. A.; Martínez-Núñez, E. HCN Elimination from Vinyl Cyanide: Product Energy Partitioning, the Role of Hydrogen–Deuterium Exchange Reactions and a New Pathway. Phys. Chem. Chem. Phys. 2015, 17, 6948– 6955, DOI: 10.1039/C4CP05626D61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXit1aquro%253D&md5=7d4dd3daa6fd88d8777f26838c395778HCN elimination from vinyl cyanide: product energy partitioning, the role of hydrogen-deuterium exchange reactions and a new pathwayVazquez, Saulo A.; Martinez-Nunez, EmilioPhysical Chemistry Chemical Physics (2015), 17 (10), 6948-6955CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The different HCN elimination pathways from vinyl cyanide (VCN) are studied in this paper using RRKM, Kinetic Monte Carlo (KMC), and quasi-classical trajectory (QCT) calcns. A new HCN elimination pathway proves to be very competitive with the traditional 3-center and 4-center mechanisms, particularly at low excitation energies. However, low excitation energies have never been exptl. explored, and the high and low excitation regions are dynamically different. The KMC simulations carried out using singly deuterated VCN (CH2=CD-CN) at 148 kcal mol-1 show the importance of hydrogen-deuterium exchange reactions: both DCN and HCN will be produced in any of the 1,1 and 1,2 elimination pathways. The QCT simulation results obtained for the 3-center pathway are in agreement with the available exptl. results, with the 4-center results showing much more excitation of the products. In general, results seem to be consistent with a photodissocn. mechanism at 193 nm, where the mol. dissocs. (at least the HCN elimination pathways) in the ground electronic state. However, simulations assume that internal conversion is a fully statistical process, i.e., the HCN elimination channels proceed on the ground electronic state according to RRKM theory, which might not be the case. In future studies it would be of interest to include the photo-prepd. electronically excited state(s) in the dynamics simulations.
- 62Martínez-Núñez, E. An Automated Method to Find Transition States Using Chemical Dynamics Simulations. J. Comput. Chem. 2015, 36, 222– 234, DOI: 10.1002/jcc.2379062https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGgtLbO&md5=e22946d4913acb912ffd139e36d6c11cAn automated method to find transition states using chemical dynamics simulationsMartinez-Nunez, EmilioJournal of Computational Chemistry (2015), 36 (4), 222-234CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)A procedure to automatically find the transition states (TSs) of a mol. system (MS) is proposed. It has two components: high-energy chem. dynamics simulations (CDS), and an algorithm that analyzes the geometries along the trajectories to find reactive pathways. Two levels of electronic structure calcns. are involved: a low level (LL) is used to integrate the trajectories and also to optimize the TSs, and a higher level (HL) is used to reoptimize the structures. The method has been tested in three MSs: formaldehyde, formic acid (FA), and vinyl cyanide (VC), using MOPAC2012 and Gaussian09 to run the LL and HL calcns., resp. Both the efficacy and efficiency of the method are very good, with around 15 TS structures optimized every 10 trajectories, which gives a total of 7, 12, and 83 TSs for formaldehyde, FA, and VC, resp. The use of CDS makes it a powerful tool to unveil possible nonstatistical behavior of the system under study. © 2014 Wiley Periodicals, Inc.
- 63Martínez-Núñez, E. An Automated Transition State Search Using Classical Trajectories Initialized at Multiple Minima. Phys. Chem. Chem. Phys. 2015, 17, 14912– 14921, DOI: 10.1039/C5CP02175H63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnslOqsLo%253D&md5=695f6ea8566cc28afe6bb7c89a434bbeAn automated transition state search using classical trajectories initialized at multiple minimaMartinez-Nunez, EmilioPhysical Chemistry Chemical Physics (2015), 17 (22), 14912-14921CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Very recently, we proposed an automated method for finding transition states of chem. reactions using dynamics simulations; the method has been termed Transition State Search using Chem. Dynamics Simulations (TSSCDS) (E. Martinez-Nunez, J. Comput. Chem., 2015, 36, 222-234). In the present work, an improved automated search procedure is developed, which consists of iteratively running different ensembles of trajectories initialized at different min. The iterative TSSCDS method is applied to the complex C3H4O system, obtaining a total of 66 different min. and 276 transition states. With the obtained transition states and paths, statistical RRKM calcns. and Kinetic Monte Carlo simulations are carried out to study the fragmentation dynamics of propenal, which is the global min. of the system. The kinetic simulations provide a (three-body dissocn.)/(CO elimination) ratio of 1.49 for an excitation energy of 148 kcal mol-1, which agrees well with the corresponding value obtained in the photolysis of propenal at 193 nm (1.1), suggesting that at least these two channels: three-body dissocn. (to give H2 + CO + C2H2) and CO elimination occur on the ground electronic state.
- 64Varela, J. A.; Vázquez, S. A.; Martínez-Núñez, E. An Automated Method to Find Reaction Mechanisms and Solve the Kinetics in Organometallic Catalysis. Chem. Sci. 2017, 8, 3843– 3851, DOI: 10.1039/C7SC00549K64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjsl2rtr8%253D&md5=df77d0eab3dac5fc42530661b1d57954An automated method to find reaction mechanisms and solve the kinetics in organometallic catalysisVarela, J. A.; Vazquez, S. A.; Martinez-Nunez, E.Chemical Science (2017), 8 (5), 3843-3851CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)A novel computational method is proposed in this work for use in discovering reaction mechanisms and solving the kinetics of transition metal-catalyzed reactions. The method does not rely on either chem.intuition or assumed a priori mechanisms, and it works in a fully automated fashion. Its core is a procedure, recently developed by one of the authors, that combines accelerated direct dynamics with an efficient geometry-based post-processing algorithm to find transition states. In the present work, several auxiliary tools have been added to deal with the specific features of transition metal catalytic reactions. As a test case, we chose the cobalt-catalyzed hydroformylation of ethylene because of its well-established mechanism, and the fact that it has already been used in previous automated computational studies. Besides the generally accepted mechanism of Heck and Breslow, several side reactions, such as hydrogenation of the alkene, emerged from our calcns. Addnl., the calcd.rate law for the hydroformylation reaction agrees reasonably well with those obtained in previous exptl.and theor.studies.
- 65Rodriguez, A.; Rodriguez-Fernandez, R.; Vazquez, S. A.; Barnes, G. L.; Stewart, J. J. P.; Martinez-Nunez, E. tsscds2018: A Code for Automated Discovery of Chemical Reaction Mechanisms and Solving the Kinetics. J. Comput. Chem. 2018, 39, 1922– 1930, DOI: 10.1002/jcc.2537065https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhslOksr7J&md5=f0374c367acd28cb3cf2ebedb5ef3eeetsscds2018: A code for automated discovery of chemical reaction mechanisms and solving the kineticsRodriguez, Aurelio; Rodriguez-Fernandez, Roberto; A. Vazquez, Saulo; L. Barnes, George; J. P. Stewart, James; Martinez-Nunez, EmilioJournal of Computational Chemistry (2018), 39 (23), 1922-1930CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)A new software, called tsscds2018, has been developed to discover reaction mechanisms and solve the kinetics in a fully automated fashion. The program employs algorithms based on Graph Theory to find transition state (TS) geometries from accelerated semiempirical dynamics simulations carried out with MOPAC2016. Then, the TSs are connected to the corresponding min. and the reaction network is obtained. Kinetic data like populations vs time or the abundancies of each product can also be obtained with our program thanks to a Kinetic Monte Carlo routine. Highly accurate ab initio potential energy diagrams and kinetics can also be obtained using an interface with Gaussian09. The source code is available on the following site: © 2018 Wiley Periodicals, Inc.
- 66Cerjan, C. J.; Miller, W. H. On Finding Transition States. J. Chem. Phys. 1981, 75, 2800– 2806, DOI: 10.1063/1.44235266https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3MXltlyqsrY%253D&md5=62bc3d736a49a1df81c3f7b428117645On finding transition statesCerjan, Charles J.; Miller, William H.Journal of Chemical Physics (1981), 75 (6), 2800-6CODEN: JCPSA6; ISSN:0021-9606.An algorithm for locating transition states on a potential energy surface is described. The most important feature of the algorithm, which makes explicit use of the second deriv. matrix of the potential surface, is that it is able to "walk uphill" from the min. on a potential surface to the transition state essentially automatically. The method is illustrated by application to a two dimensional model problem, to the vinylidene-acetylene rearrangement (H2C = C:↔HC≡CH), and to the dissocn. and rearrangement of formaldehyde (H2CO↔H2 + O, HCOH). The algorithm is also seen to provide an improved way of following a reaction path from a transition state down to reactants or products.
- 67Simons, J.; Joergensen, P.; Taylor, H.; Ozment, J. Walking on Potential Energy Surfaces. J. Phys. Chem. 1983, 87, 2745– 2753, DOI: 10.1021/j100238a01367https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3sXksF2it74%253D&md5=af251d7a8647c328879862fd7cde68a3Walking on potential energy surfacesSimons, Jack; Joergensen, Poul; Taylor, Hugh; Ozment, JudyJournal of Physical Chemistry (1983), 87 (15), 2745-53CODEN: JPCHAX; ISSN:0022-3654.By combining a local quadratic approxn. to the potential energy surface with the concept of a trust radius within which this quadratic approxn. is accurate and a scaling of one active coordinate, an automated surface walking algorithm was developed. This algorithm allows one to walk from geometries characteristic of equil. mol. structures, uphill along stream beds, through transition-state geometries, and onward to product-mol. equil. geometries. The method was appled to model and ab initio test cases with encouraging results. The success of using the algorithm in connection with approx. Hessian matrixes formed via so-called update techniques, which require only local force information, is esp. encouraging in light of the high cost of ab initio anal. evaluation of the Hessian.
- 68Davis, H. L.; Wales, D. J.; Berry, R. S. Exploring Potential Energy Surfaces with Transition State Calculations. J. Chem. Phys. 1990, 92, 4308– 4319, DOI: 10.1063/1.45779068https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3cXit1elu74%253D&md5=c2ae2665bcc5e23802f289641cd94e3cExploring potential energy surfaces with transition state calculationsDavis, Heidi L.; Wales, David J.; Berry, R. StephenJournal of Chemical Physics (1990), 92 (7), 4308-19CODEN: JCPSA6; ISSN:0021-9606.Means are presented for using stationary points in two ways. One, for well-understood potentials, elucidates relations between the form of the surface and the dynamics that it supports, including the detn. of the effective mol. symmetry group. The other, for potentials of uncertain quality, provides a test for unphys. characteristics and suggests how the surface might be improved if it is found to be unsatisfactory in some respect. Our approach involves comparison of transition-state calcns. using the slowest-slide and Cerjan-Miller algorithms for two systems: the Lennard-Jones Ar7 cluster, and the Handy-Carter many-body-expansion potential for the ground state of formaldehyde.
- 70Wales, D. J. Locating Stationary Points for Clusters in Cartesian Coordinates. J. Chem. Soc., Faraday Trans. 1993, 89, 1305– 1313, DOI: 10.1039/ft993890130570https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXksFKmu78%253D&md5=b823814bb89c8e62b4e904ae2d37b45dLocating stationary points for clusters in cartesian coordinatesWales, David J.Journal of the Chemical Society, Faraday Transactions (1993), 89 (9), 1305-13,4 platesCODEN: JCFTEV; ISSN:0956-5000.Location of min. and transition states on a potential energy surface by the eigenvector-following method using Cartesian coordinates and a projection operator is described. Comparisons with calcns. employing std. internal coordinates are made for a wide variety of model clusters. The new method, suggested by Baker and Hehre (1991), generally produces faster convergence and solves a no. of problems that are inherent when using distance, bond angle, and dihedral angle internal coordinates. In particular, eigenvector-following calcns. using analytic first and second energy derivs. should now be possible for much larger systems. Some example reaction paths are illustrated, including a new facetting rearrangement of 55- and 147-atom Mackay icosahedra. The basins of attraction of min. and transition states are also calcd., i.e., the regions of the potential-energy surface for which stationary-point searches converge to a given structure. The superiority of the projection operator approach is again demonstrated, and the previous observation that initial geometrical contraction is helpful in transition-state searches is confirmed.
- 72Doye, J. P. K.; Wales, D. J. Surveying a Potential Energy Surface by Eigenvector-Following. Z. Phys. D: At., Mol. Clusters 1997, 40, 194– 197, DOI: 10.1007/s00460005019272https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXjs12rtrw%253D&md5=affb326a8ca9636d1e24e1b5937b840eSurveying a potential energy surface by eigenvector-following. Applications to global optimization and the structural transformations of clustersDoye, J. P. K.; Wales, D. J.Zeitschrift fuer Physik D: Atoms, Molecules and Clusters (1997), 40 (1-4), 194-197CODEN: ZDACE2; ISSN:0178-7683. (Springer)We have developed a method to search potential energy surfaces which avoids some of the difficulties assocd. with trapping in local min. Steps are directly taken between min. using eigenvector-following. Exploration of this space by low temp. Metropolis Monte Carlo is a useful global optimization tool. This method successfully finds the lowest energy icosahedral min. of Lennard-Jones clusters from random starting configurations, but cannot find the global min. in a reasonable time for difficult cases such as the 38-atom Lennard-Jones cluster where the face-centered-cubic truncated octahedron is lowest in energy. However, by performing searches at higher temps., we have found a pathway between the truncated octahedron and the lowest energy icosahedral min. Such a pathway may be illustrative of some of the structural transformations that are obsd. for supported metal clusters by electron microscopy.
- 74Munro, L. J.; Wales, D. J. Defect Migration in Crystalline Silicon. Phys. Rev. B: Condens. Matter Mater. Phys. 1999, 59, 3969– 3980, DOI: 10.1103/PhysRevB.59.396974https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXosVeltw%253D%253D&md5=a958a13eef54db0261a60a64d4e77e87Defect migration in crystalline siliconMunro, Lindsey J.; Wales, David J.Physical Review B: Condensed Matter and Materials Physics (1999), 59 (6), 3969-3980CODEN: PRBMDO; ISSN:0163-1829. (American Physical Society)A no. of vacancy and interstitial defect migration mechanisms were characterized for cryst. Si using supercells contg. 64 and 216 atoms and a tight-binding approach. The authors study various defect configurations corresponding to min. and the pathways that connect them. A modified eigenvector-following approach was used to locate true transition states. The authors exploit the fact that only one Hessian eigenvector is needed to define the uphill search direction and use conjugate gradient minimization in the tangent space to produce a hybrid algorithm. Two implementations of this approach are considered, the 1st where 2nd derivs. are available but full diagonalization of the Hessian would be the most time-consuming step, and the 2nd where only 1st derivs. of the energy are known.
- 75Malek, R.; Mousseau, N. Dynamics of Lennard-Jones Clusters: A Characterization of the Activation-Relaxation Technique. Phys. Rev. E: Stat. Phys., Plasmas, Fluids, Relat. Interdiscip. Top. 2000, 62, 7723– 7728, DOI: 10.1103/PhysRevE.62.772375https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXoslahurw%253D&md5=73391e2c5502b4312a8cdd0f07852b91Dynamics of Lennard-Jones clusters: A characterization of the activation-relaxation techniqueMalek, Rachid; Mousseau, NormandPhysical Review E: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics (2000), 62 (6-A), 7723-7728CODEN: PLEEE8; ISSN:1063-651X. (American Physical Society)The potential energy surface of Lennard-Jones clusters is investigated using the activation-relaxation technique (ART). This method defines events in the configurational energy landscape as a two-step process: (a) a configuration is first activated from a local min. to a nearby saddle-point, and (b) is then relaxed to a new min. Although ART has been applied with success to a wide range of materials such as a-Si, a-SiO2, and binary Lennard-Jones glasses, questions remain regarding the biases of the technique. We address some of these questions in a detailed study of ART-generated events in Lennard-Jones clusters, a system for which much is already known. In particular, we study the distribution of saddle-points, the pathways between configurations, and the reversibility of paths. We find that ART can identify all trajectories with a first-order saddle point leaving a given min., is fully reversible, and samples events following the Boltzmann wt. at the saddle point.
- 76Deglmann, P.; Furche, F. Efficient Characterization of Stationary Points on Potential Energy Surfaces. J. Chem. Phys. 2002, 117, 9535– 9538, DOI: 10.1063/1.152339376https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XovVSru78%253D&md5=3bbd5b3b826d7210588dbb7121b72176Efficient characterization of stationary points on potential energy surfacesDeglmann, Peter; Furche, FilippJournal of Chemical Physics (2002), 117 (21), 9535-9538CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Traditional methods for characterizing an optimized mol. structure as a min. or as a saddle point on the nuclear potential energy surface require the full Hessian. However, if f denotes the no. of nuclear degrees of freedom, a full Hessian calcn. is more expensive than a single point geometry optimization step by the order of magnitude of f. Here we present a method which allows to det. the lowest vibrational frequencies of a mol. at significantly lower cost. Our approach takes advantage of the fact that only a few perturbed first-order wave functions need to be computed in an iterative diagonalization scheme instead of f ones in a full Hessian calcn. We outline an implementation for Hartree-Fock and d. functional methods. Applications indicate a scaling similar to that of a single point energy or gradient calcn., but with a larger prefactor. Depending on the no. of soft vibrational modes, the iterative method becomes effective for systems with more than 30-50 atoms.
- 77Reiher, M.; Neugebauer, J. A Mode-Selective Quantum Chemical Method for Tracking Molecular Vibrations Applied to Functionalized Carbon Nanotubes. J. Chem. Phys. 2003, 118, 1634– 1641, DOI: 10.1063/1.152390877https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjtVaquw%253D%253D&md5=616ea82fd0a616e1c7c6428c4581da7bA mode-selective quantum chemical method for tracking molecular vibrations applied to functionalized carbon nanotubesReiher, Markus; Neugebauer, JohannesJournal of Chemical Physics (2003), 118 (4), 1634-1641CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The theor. investigation of mesoscopic objects requires new techniques which are particularly suited for the study of selected aspects of these systems. Vibrational spectroscopy is a main source for structural information on heterogeneous systems. We present an efficient quantum chem. method, which relies on a modified Davidson algorithm for targeting selected vibrations in IR and Raman spectra. This approach is applied to the characteristic breathing modes of single-walled carbon nanotubes.
- 79Bergeler, M.; Herrmann, C.; Reiher, M. Mode-Tracking Based Stationary-Point Optimization. J. Comput. Chem. 2015, 36, 1429– 1438, DOI: 10.1002/jcc.2395879https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXpvFWgt7c%253D&md5=50ae502b58d1b2eb8f04225407e085afMode-tracking based stationary-point optimizationBergeler, Maike; Herrmann, Carmen; Reiher, MarkusJournal of Computational Chemistry (2015), 36 (19), 1429-1438CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)In this work, we present a transition-state optimization protocol based on the Mode-Tracking algorithm [Reiher and Neugebauer, J. Chem. Phys., 2003, 118, 1634]. By calcg. only the eigenvector of interest instead of diagonalizing the full Hessian matrix and performing an eigenvector following search based on the selectively calcd. vector, we can efficiently optimize transition-state structures. The initial guess structures and eigenvectors are either chosen from a linear interpolation between the reactant and product structures, from a nudged-elastic band search, from a constrained-optimization scan, or from the min.-energy structures. Alternatively, initial guess vectors based on chem. intuition may be defined. We then iteratively refine the selected vectors by the Davidson subspace iteration technique. This procedure accelerates finding transition states for large mols. of a few hundred atoms. It is also beneficial in cases where the starting structure is very different from the transition-state structure or where the desired vector to follow is not the one with lowest eigenvalue. Explorative studies of reaction pathways are feasible by following manually constructed mol. distortions. © 2015 Wiley Periodicals, Inc.
- 80Halgren, T. A.; Lipscomb, W. N. The Synchronous-Transit Method for Determining Reaction Pathways and Locating Molecular Transition States. Chem. Phys. Lett. 1977, 49, 225– 232, DOI: 10.1016/0009-2614(77)80574-580https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE2sXlsFWmtLs%253D&md5=90c0d95b096220fddcc7eebc0639fdfdThe synchronous-transit method for determining reaction pathways and locating molecular transition statesHalgren, Thomas A.; Lipscomb, William N.Chemical Physics Letters (1977), 49 (2), 225-32CODEN: CHPLBC; ISSN:0009-2614.In the synchronous-transit method, a model linear synchronous transit pathway is first constructed and is then refined by optimizing 1 or more intermediate structures subject to the constraint that the optimized structure retain the same relative position along the path orthogonal optimization. The method yields a series of energy ests. which progressively bound the energy of the transition state from above and from below. High computational efficiency is attainable, and sufficient flexibility is provided to deal with asynchronous processes. Comparisons are made to the alternative reaction-coordinate approach. The method is applied to a model 2-dimensional energy surface and to the allowed electrocyclic interconversions of the cyclopropyl and allyl cations and of cyclobutene and cis-butadiene.
- 81Ayala, P. Y.; Schlegel, H. B. A Combined Method for Determining Reaction Paths, Minima, and Transition State Geometries. J. Chem. Phys. 1997, 107, 375– 384, DOI: 10.1063/1.47439881https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXksVeksrY%253D&md5=2ec17a4bf9a0f0f848e6fe0b844fe250A combined method for determining reaction paths, minima, and transition state geometriesAyala, Philippe Y.; Schlegel, H. BernhardJournal of Chemical Physics (1997), 107 (2), 375-384CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Mapping out a reaction mechanism involves optimizing the reactants and products, finding the transition state and following the reaction path connecting them. Transition states can be difficult to locate and reaction paths can be expensive to follow. We describe an efficient algorithm for detg. the transition state, min. and reaction path in a single procedure. Starting with an approx. path represented by N points, the path is iteratively relaxed until one of the N points reached the transition state, the end points optimize to min. and the remaining points converged to a second order approxn. of the steepest descent path. The method appears to be more reliable than conventional transition state optimization algorithms, and requires only energies and gradients, but not second deriv. calcns. The procedure is illustrated by application to a no. of model reactions. In most cases, the reaction mechanism can be described well using 5 to 7 points to represent the transition state, the min. and the path. The computational cost of relaxing the path is less than or comparable to the cost of std. techniques for finding the transition state and the min., detg. the transition vector and following the reaction path on both sides of the transition state.
- 82Henkelman, G.; Jónsson, H. A Dimer Method for Finding Saddle Points on High Dimensional Potential Surfaces Using Only First Derivatives. J. Chem. Phys. 1999, 111, 7010– 7022, DOI: 10.1063/1.48009782https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXmt1Ojurc%253D&md5=d3628bc9e56615b91730dd2224a36723A dimer method for finding saddle points on high dimensional potential surfaces using only first derivativesHenkelman, Graeme; Jonsson, HannesJournal of Chemical Physics (1999), 111 (15), 7010-7022CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The problem of detg. which activated (and slow) transitions can occur from a given initial state at a finite temp. is addressed. In the harmonic approxn. to transition state theory this problem reduces to finding the set of low lying saddle points at the boundary of the potential energy basin assocd. with the initial state, as well as the relevant vibrational frequencies. Also, when full transition state theory calcns. are carried out, it can be useful to know the location of the saddle points on the potential energy surface. A method for finding saddle points without knowledge of the final state of the transition is described. The method only makes use of first derivs. of the potential energy and is, therefore, applicable in situations where second derivs. are too costly or too tedious to evaluate, for example, in plane wave based d. functional theory calcns. It is also designed to scale efficiently with the dimensionality of the system and can be applied to very large systems when empirical or semiempirical methods are used to obtain the at. forces. The method can be started from the potential min. representing the initial state, or from an initial guess closer to the saddle point. An application to Al adatom diffusion on an Al(100) surface described by an embedded atom method potential is presented. A large no. of saddle points were found for adatom diffusion and dimer/vacancy formation. A surprisingly low energy four atom exchange process was found as well as processes indicative of local hex reconstruction of the surface layer.
- 83Henkelman, G.; Uberuaga, B. P.; Jónsson, H. A Climbing Image Nudged Elastic Band Method for Finding Saddle Points and Minimum Energy Paths. J. Chem. Phys. 2000, 113, 9901– 9904, DOI: 10.1063/1.132967283https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFagurc%253D&md5=3899b9e2e9e3eb74009987d96623f018A climbing image nudged elastic band method for finding saddle points and minimum energy pathsHenkelman, Graeme; Uberuaga, Blas P.; Jonsson, HannesJournal of Chemical Physics (2000), 113 (22), 9901-9904CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)A modification of the nudged elastic band method for finding min. energy paths is presented. One of the images is made to climb up along the elastic band to converge rigorously on the highest saddle point. Also, variable spring consts. are used to increase the d. of images near the top of the energy barrier to get an improved est. of the reaction coordinate near the saddle point. Applications to CH4 dissociative adsorption on Ir(111) and H2 on Si(100) using plane wave based d. functional theory are presented.
- 84Henkelman, G.; Jónsson, H. Improved Tangent Estimate in the Nudged Elastic Band Method for Finding Minimum Energy Paths and Saddle Points. J. Chem. Phys. 2000, 113, 9978– 9985, DOI: 10.1063/1.132322484https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFagu7Y%253D&md5=57dbeadabf6061460912090f40b581e0Improved tangent estimate in the nudged elastic band method for finding minimum energy paths and saddle pointsHenkelman, Graeme; Jonsson, HannesJournal of Chemical Physics (2000), 113 (22), 9978-9985CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)An improved way of estg. the local tangent in the nudged elastic band method for finding min. energy paths is presented. In systems where the force along the min. energy path is large compared to the restoring force perpendicular to the path and when many images of the system are included in the elastic band, kinks can develop and prevent the band from converging to the min. energy path. We show how the kinks arise and present an improved way of estg. the local tangent which solves the problem. The task of finding an accurate energy and configuration for the saddle point is also discussed and examples given where a complementary method, the dimer method, is used to efficiently converge to the saddle point. Both methods only require the first deriv. of the energy and can, therefore, easily be applied in plane wave based d.-functional theory calcns. Examples are given from studies of the exchange diffusion mechanism in a Si crystal, Al addimer formation on the Al(100) surface, and dissociative adsorption of CH4 on an Ir(111) surface.
- 85Maragakis, P.; Andreev, S. A.; Brumer, Y.; Reichman, D. R.; Kaxiras, E. Adaptive Nudged Elastic Band Approach for Transition State Calculation. J. Chem. Phys. 2002, 117, 4651– 4658, DOI: 10.1063/1.149540185https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmsVWntbo%253D&md5=9645dcee50aacfef2aa9265a1989ac1eAdaptive nudged elastic band approach for transition state calculationMaragakis, P.; Andreev, Stefan A.; Brumer, Yisroel; Reichman, David R.; Kaxiras, EfthimiosJournal of Chemical Physics (2002), 117 (10), 4651-4658CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)We present a method for the location of transition states in complicated phys. systems. Our algorithm is a variation of the well-established nudged elastic band method and leads to significant improvements in efficiency and accuracy. We assess the applicability of our method by testing it on several systems of practical interest representing a variety of phys. situations. At the mol. level, we apply the method to tautomerization processes in nucleic acid bases and the double proton transfer in nucleic acid base pairs. For bulk systems, we considered the concerted exchange mechanism in Si, which is a complicated pathway for defect-free diffusion in the diamond lattice. For surface systems, we considered ad-dimer diffusion mechanisms on Si(100). We incorporated the climbing image extension of the nudged elastic band method and compared it against the original approach on two-dimensional model potential energy surfaces. Based on favorable comparisons with related methods and the general implementation of our method, we believe that this is well suited for efficient ests. of activation barriers with sophisticated electronic structure codes.
- 86E, W.; Ren, W.; Vanden-Eijnden, E. String Method for the Study of Rare Events. Phys. Rev. B: Condens. Matter Mater. Phys. 2002, 66, 052301, DOI: 10.1103/PhysRevB.66.05230186https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmvVSlurg%253D&md5=1c24a86bf403c333e9705f00876e4aa3String method for the study of rare eventsE, Weinan; Ren, Weiqing; Vanden-Eijnden, EricPhysical Review B: Condensed Matter and Materials Physics (2002), 66 (5), 052301/1-052301/4CODEN: PRBMDO; ISSN:0163-1829. (American Physical Society)We present an efficient method for computing the transition pathways, free energy barriers, and transition rates in complex systems with relatively smooth energy landscapes. The method proceeds by evolving strings, i.e., smooth curves with intrinsic parametrization whose dynamics takes them to the most probable transition path between two metastable regions in configuration space. Free energy barriers and transition rates can then be detd. by a std. umbrella sampling around the string. Applications to Lennard-Jones cluster rearrangement and thermally induced switching of a magnetic film are presented.
- 87E, W.; Ren, W.; Vanden-Eijnden, E. Finite Temperature String Method for the Study of Rare Events. J. Phys. Chem. B 2005, 109, 6688– 6693, DOI: 10.1021/jp045543087https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtFSnsbo%253D&md5=f92a743d5d4b946756c04c6c1cbc8a8dFinite Temperature String Method for the Study of Rare EventsE, Weinan; Ren, Weiqing; Vanden-Eijnden, EricJournal of Physical Chemistry B (2005), 109 (14), 6688-6693CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)A method is presented for the study of rare events such as conformational changes arising in activated processes whose reaction coordinate is not known beforehand and for which the assumptions of transition state theory are invalid. The method samples the energy landscape adaptively and dets. the isoprobability surfaces for the transition: by definition the trajectories initiated anywhere on one of these surfaces has equal probability to reach first one metastable set rather than the other. Upon weighting these surfaces by the equil. probability distribution, one obtains an effective transition pathway, i.e., a tube in configuration space inside which conformational changes occur with high probability, and the assocd. rate. The method is first validated on a simple two-dimensional example; then it is applied to a model of solid-solid transformation of a condensed system.
- 88Behn, A.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Efficient Exploration of Reaction Paths via a Freezing String Method. J. Chem. Phys. 2011, 135, 224108, DOI: 10.1063/1.366490188https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1SkurrN&md5=01c0f45d3455f92d1341022377717530Efficient exploration of reaction paths via a freezing string methodBehn, Andrew; Zimmerman, Paul M.; Bell, Alexis T.; Head-Gordon, MartinJournal of Chemical Physics (2011), 135 (22), 224108/1-224108/9CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The ability to efficiently locate transition states is critically important to the widespread adoption of theor. chem. techniques for their ability to accurately predict kinetic consts. Existing surface walking techniques to locate such transition states typically require an extremely good initial guess that is often beyond intuition to est. To alleviate this problem, automated techniques to locate transition state guesses have been created that take the known reactant and product endpoint structures as inputs. In this work, we present a simple method to build an approx. reaction path through a combination of interpolation and optimization. Starting from the known reactant and product structures, new nodes are interpolated inwards towards the transition state, partially optimized orthogonally to the reaction path, and then frozen before a new pair of nodes is added. The algorithm is stopped once the string ends connect. For the practical user, this method provides a quick and convenient way to generate transition state structure guesses. Tests on three reactions (cyclization of cis,cis-2,4-hexadiene, alanine dipeptide conformation transition, and ethylene dimerization in a Ni-exchanged zeolite) show that this "freezing string" method is an efficient way to identify complex transition states with significant cost savings over existing methods, particularly when high quality linear synchronous transit interpolation is employed. (c) 2011 American Institute of Physics.
- 89Behn, A.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Incorporating Linear Synchronous Transit Interpolation into the Growing String Method: Algorithm and Applications. J. Chem. Theory Comput. 2011, 7, 4019– 4025, DOI: 10.1021/ct200654u89https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOqurjE&md5=f76c6427d713c0375114e0262ef0d29eIncorporating Linear Synchronous Transit Interpolation into the Growing String Method: Algorithm and ApplicationsBehn, Andrew; Zimmerman, Paul M.; Bell, Alexis T.; Head-Gordon, MartinJournal of Chemical Theory and Computation (2011), 7 (12), 4019-4025CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The growing string method is a powerful tool in the systematic study of chem. reactions with theor. methods which allows for the rapid identification of transition states connecting known reactant and product structures. However, the efficiency of this method is heavily influenced by the choice of interpolation scheme when adding new nodes to the string during optimization. In particular, the use of Cartesian coordinates with cubic spline interpolation often produces guess structures which are far from the final reaction path and require many optimization steps (and thus many energy and gradient calcns.) to yield a reasonable final structure. In this paper, we present a new method for interpolating and reparameterizing nodes within the growing string method using the linear synchronous transit method of Halgren and Lipscomb. When applied to the alanine dipeptide rearrangement and a simplified cationic alkyl ring condensation reaction, a significant speedup in terms of computational cost is achieved (30-50%).
- 90Zimmerman, P. Reliable Transition State Searches Integrated with the Growing String Method. J. Chem. Theory Comput. 2013, 9, 3043– 3050, DOI: 10.1021/ct400319w90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXptFeht78%253D&md5=6f5715237172541a74de71a1781cee83Reliable Transition State Searches Integrated with the Growing String MethodZimmerman, PaulJournal of Chemical Theory and Computation (2013), 9 (7), 3043-3050CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The growing string method (GSM) is highly useful for locating reaction paths connecting two mol. intermediates. GSM has often been used in a two-step procedure to locate exact transition states (TS), where GSM creates a quality initial structure for a local TS search. This procedure and others like it, however, do not always converge to the desired transition state because the local search is sensitive to the quality of the initial guess. This article describes an integrated technique for simultaneous reaction path and exact transition state search. This is achieved by implementing an eigenvector following optimization algorithm in internal coordinates with Hessian update techniques. After partial convergence of the string, an exact saddle point search begins under the constraint that the maximized eigenmode of the TS node Hessian has significant overlap with the string tangent near the TS. Subsequent optimization maintains connectivity of the string to the TS as well as locks in the TS direction, all but eliminating the possibility that the local search leads to the wrong TS. To verify the robustness of this approach, reaction paths and TSs are found for a benchmark set of more than 100 elementary reactions.
- 91Vaucher, A. C.; Reiher, M. Minimum Energy Paths and Transition States by Curve Optimization. J. Chem. Theory Comput. 2018, 14, 3091– 3099, DOI: 10.1021/acs.jctc.8b0016991https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXnsF2qtbg%253D&md5=88c0d81d005d0b913d9b75341576889dMinimum Energy Paths and Transition States by Curve OptimizationVaucher, Alain C.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (6), 3091-3099CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Transition states and min. energy paths are essential to understand and predict chem. reactivity. Double-ended methods represent a std. approach for their detn. A new double-ended method that optimizes reaction paths described by curves is introduced. Unlike other methods, the approach optimizes the curve parameters rather than distinct structures along the path. With mol. paths represented as continuous curves, the optimization can benefit from the advantages of an integral-based formulation. This approach is called ReaDuct and its applicability for mol. paths parametrized by B-spline curves is demonstrated.
- 92Broadbelt, L. J.; Stark, S. M.; Klein, M. T. Computer Generated Pyrolysis Modeling: On-the-Fly Generation of Species, Reactions, and Rates. Ind. Eng. Chem. Res. 1994, 33, 790– 799, DOI: 10.1021/ie00028a00392https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXitFKnu7s%253D&md5=7cfd4d0b5f978bbea1c40e00eadcbf77Computer Generated Pyrolysis Modeling: On-the-Fly Generation of Species, Reactions, and RatesBroadbelt, Linda J.; Stark, Scott M.; Klein, Michael T.Industrial & Engineering Chemistry Research (1994), 33 (4), 790-9CODEN: IECRED; ISSN:0888-5885.The development of an integrated system for the computer generation of kinetic models is described. Required input is the structure of the reactants, the reaction rules, and the parameters of a structure/property kinetics correlation. The algorithm transforms this information into reactant/product relationships, i.e., the reaction network, species properties, rate consts., and the FORTRAN code corresponding to the governing species' balance equations, and offers a soln. capability. Graph theory is exploited to represent the constituent atoms of a mol. to allow detn. of species' uniqueness, implement chem. reactions, and identify reaction products. Special attention was devoted to improved algorithm efficiencies, the handling of ring systems, and "on-the-fly" quantum chem. calcns. This general approach is described in using ethane and cyclohexane pyrolysis case studies. The increase in the no. of equations and no. of components for ethane pyrolysis was exponential with the carbon no. of allowed species.
- 93Broadbelt, L. J.; Stark, S. M.; Klein, M. T. Computer Generated Reaction Modelling: Decomposition and Encoding Algorithms for Determining Species Uniqueness. Comput. Chem. Eng. 1996, 20, 113– 129, DOI: 10.1016/0098-1354(94)00009-D93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXps1yjsL0%253D&md5=12e4ffb130284518319665befc664e09Computer generated reaction modeling: decomposition and encoding algorithms for determining species uniquenessBroadbelt, L. J.; Stark, S. M.; Klein, M. T.Computers & Chemical Engineering (1996), 20 (2), 113-29CODEN: CCENDW; ISSN:0098-1354. (Elsevier)The concept of computer generated reaction modeling was broadened through the development of a general planar graph algorithm for detn. of isomorphism. The previous capability was limited by its inability to det. the uniqueness of ring-contg. species unambiguously, restricting the application of automatic network generation to non-cyclic species or cyclic species where the ring was not involved in the chem. transformation. In this work, the systematic identification of both noncyclic and cyclic species was carried out by constructing the structurally explicit decompn. tree, an assembly of the biconnected components of the graph, from which a graph invariant unique string code was obtained by iteratively encoding and ordering the subtrees of the decompn. tree. A lexicog. comparison of the unique string code of the candidate species with the string codes of all previously generated species with the same empirical formula allowed unambiguous detn. of species uniqueness.
- 94Broadbelt, L. J.; Pfaendtner, J. Lexicography of Kinetic Modeling of Complex Reaction Networks. AIChE J. 2005, 51, 2112– 2121, DOI: 10.1002/aic.1059994https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslCnt7c%253D&md5=47e8076ea9b3fde03f4c063e018a1131Lexicography of kinetic modeling of complex reaction networksBroadbelt, Linda J.; Pfaendtner, JimAIChE Journal (2005), 51 (8), 2112-2121CODEN: AICEAC; ISSN:0001-1541. (John Wiley & Sons, Inc.)Lexicog. of kinetic modeling of complex reaction networks is discussed.
- 95Evans, M. G.; Polanyi, M. Inertia and Driving Force of Chemical Reactions. Trans. Faraday Soc. 1938, 34, 11– 24, DOI: 10.1039/tf938340001195https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaA1cXitVWisg%253D%253D&md5=1b35420fa6bfc7cd2c1118fb7a7096ebInertia and driving force of chemical reactionsEvans, M. G.; Polanyi, M.Transactions of the Faraday Society (1938), 34 (), 11-24CODEN: TFSOA4; ISSN:0014-7672.A reaction has "inertia" if the activation energy is exothermic and has a "driving force" when the formation of new bonds lowers the activation energy. The energy surfaces of the initial and final states and the reaction paths between them as well as their relation to at. repulsions are considered.
- 96Matheu, D. M.; Dean, A. M.; Grenda, J. M.; Green, W. H. Mechanism Generation with Integrated Pressure Dependence: A New Model for Methane Pyrolysis. J. Phys. Chem. A 2003, 107, 8552– 8565, DOI: 10.1021/jp034595796https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXnsVehtLk%253D&md5=087a6a72c1556f599dbf81547530cddeMechanism Generation with Integrated Pressure Dependence: A New Model for Methane PyrolysisMatheu, David M.; Dean, Anthony M.; Grenda, Jeffrey M.; Green, William H., Jr.Journal of Physical Chemistry A (2003), 107 (41), 8552-8565CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Autocatalytic, lower-temp. (≤1100 K) methane pyrolysis has defied mechanistic explanation for almost three decades. The most recent attempt (by Dean in 1990) invoked the chem. activated addn. of an allyl radical to acetylene, leading to a cyclopentadiene/cyclopentadienyl chain-branching system that prompted the obsd. autocatalysis. However, newer, more accurate thermochem. data for the cyclopentadienyl radical render that explanation untenable. A new model for methane pyrolysis is constructed here, using a novel mechanism generation approach that automatically computes any needed rate consts. k(T,P) for chem. or thermally activated pressure-dependent reactions. The computer-generated mechanism accurately predicts the obsd. autocatalysis and concn. profiles without any adjustable parameters. Radical-forming reverse disproportionation reactions-which involve propyne, allene, and fulvene-account for at least half of the exptl. obsd. autocatalytic effect. Many of these reverse disproportionations were neglected in previous studies. The cyclopentadienyl radical is also important, but it is formed primarily by the chem. activated reaction of propargyl with acetylene. New rate ests. for unimol. ring-closure reactions of unsatd. radicals are also presented. This approach is the first to incorporate pressure-dependent reactions generally and systematically during computerized mechanism construction. It successfully identifies complex but crit. chem.-reaction pathways and autocatalytic loops missed by experienced kineticists.
- 97Gao, C. W.; Allen, J. W.; Green, W. H.; West, R. H. Reaction Mechanism Generator: Automatic Construction of Chemical Kinetic Mechanisms. Comput. Phys. Commun. 2016, 203, 212– 225, DOI: 10.1016/j.cpc.2016.02.01397https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xjs12kur4%253D&md5=3403c82513d617761ce38eb7de35c5c3Reaction Mechanism Generator: Automatic construction of chemical kinetic mechanismsGao, Connie W.; Allen, Joshua W.; Green, William H.; West, Richard H.Computer Physics Communications (2016), 203 (), 212-225CODEN: CPHCBZ; ISSN:0010-4655. (Elsevier B.V.)Reaction Mechanism Generator (RMG) constructs kinetic models composed of elementary chem. reaction steps using a general understanding of how mols. react. Species thermochem. is estd. through Benson group additivity and reaction rate coeffs. are estd. using a database of known rate rules and reaction templates. At its core, RMG relies on two fundamental data structures: graphs and trees. Graphs are used to represent chem. structures, and trees are used to represent thermodn. and kinetic data. Models are generated using a rate-based algorithm which excludes species from the model based on reaction fluxes. RMG can generate reaction mechanisms for species involving carbon, hydrogen, oxygen, sulfur, and nitrogen. It also has capabilities for estg. transport and solvation properties, and it automatically computes pressure-dependent rate coeffs. and identifies chem.-activated reaction paths. RMG is an object-oriented program written in Python, which provides a stable, robust programming architecture for developing an extensible and modular code base with a large suite of unit tests. Computationally intensive functions are cythonized for speed improvements.
- 98Harper, M. R.; Van Geem, K. M.; Pyl, S. P.; Marin, G. B.; Green, W. H. Comprehensive Reaction Mechanism for N-Butanol Pyrolysis and Combustion. Combust. Flame 2011, 158, 16– 41, DOI: 10.1016/j.combustflame.2010.06.00298https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVWht7zI&md5=73235ccdbc0fdce97f3c1a8b423bc3bbComprehensive reaction mechanism for n-butanol pyrolysis and combustionHarper, Michael R.; Van Geem, Kevin M.; Pyl, Steven P.; Marin, Guy B.; Green, William H.Combustion and Flame (2011), 158 (1), 16-41CODEN: CBFMAO; ISSN:0010-2180. (Elsevier B.V.)A detailed reaction mechanism for n-butanol, consisting of 263 species and 3381 reactions, has been generated using the open-source software package, Reaction Mechanism Generator (RMG). The mechanism is tested against recently published data - jet-stirred reactor mole fraction profiles, opposed-flow diffusion flame mole fraction profiles, autoignition delay times, and doped methane diffusion flame mole fraction profiles - and newly acquired n-butanol pyrolysis expts. with very encouraging results. The chem. of butanal is also validated against autoignition delay times obtained in shock tube expts. A flux and sensitivity anal. for each simulated dataset is discussed and reveals important reactions where more accurate rate const. ests. were required. New rate const. expressions were computed using quantum chem. and transition state theory calcns. Furthermore, in addn. to comparing the proposed model with the eight datasets, the model is also compared with recently published n-butanol models for three of the datasets. Key differences between the proposed model and the published models are discussed.
- 99van Geem, K. M.; Reyniers, M.-F.; Marin, G. B.; Song, J.; Green, W. H.; Matheu, D. M. Automatic Reaction Network Generation Using RMG for Steam Cracking of N-hexane. AIChE J. 2006, 52, 718– 730, DOI: 10.1002/aic.1065599https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xht1Ogu7s%253D&md5=d20f9949dd0516d2ef7b2bba4d919fa5Automatic reaction network generation using RMG for steam cracking of n-hexaneVan Geem, Kevin M.; Reyniers, Marie-Francoise; Marin, Guy B.; Song, Jing; Green, William H.; Matheu, David M.AIChE Journal (2006), 52 (2), 718-730CODEN: AICEAC; ISSN:0001-1541. (John Wiley & Sons, Inc.)A new reaction mechanism generator RMG is used to automatically construct a pressure dependent kinetic model for the steam cracking of n-hexane. Comparison between simulated and pilot plant data shows that RMG is able to generate detailed reaction networks that accurately predict the conversion and the yields of the major products although none of the kinetic parameters are fit to the expts. RMG generates reaction networks based on minimal assumptions, making it possible to test commonly used assumptions such as the μ-hypothesis and the quasi steady-state approxn. (QSSA) for μ-radicals, traditionally used in steam cracking,1,2 as well as in pyrolysis. The RMG-reaction network for n-hexane confirms that no bimol. reactions of heavy radical species are important at the examd. conditions (COT: 953 K - 1090 K; COP: 0.20 MPa -0.24 MPa; <80% conversion), and that the QSSA for the group of μ-radicals leads to negligible errors. RMG also offers the possibility to est. the error introduced by neglecting the pressure dependence of most of the reactions. In the case studied, this frequently made (but seldom tested) approxn. appears to be justified.
- 100Petway, S. V.; Ismail, H.; Green, W. H.; Estupiñán, E. G.; Jusinski, L. E.; Taatjes, C. A. Measurements and Automated Mechanism Generation Modeling of OH Production in Photolytically Initiated Oxidation of the Neopentyl Radical. J. Phys. Chem. A 2007, 111, 3891– 3900, DOI: 10.1021/jp0668549100https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXkt1Ortrk%253D&md5=65ea9d850eea1b016f8f57d241479b04Measurements and Automated Mechanism Generation Modeling of OH Production in Photolytically Initiated Oxidation of the Neopentyl RadicalPetway, Sarah V.; Ismail, Huzeifa; Green, William H.; Estupinan, Edgar G.; Jusinski, Leonard E.; Taatjes, Craig A.Journal of Physical Chemistry A (2007), 111 (19), 3891-3900CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Prodn. of OH in the reaction of the neopentyl radical with O2 has been measured by a laser photolysis/cw absorption method for various pressures and oxygen concns. at 673, 700, and 725 K. The MIT Reaction Mechanism Generator (RMG) was used to automatically generate a model for this system, and the predicted OH concn. profiles are compared to present and literature exptl. results. Several reactions significantly affect the OH profile. The exptl. data provide useful constraints on the rate coeff. for the formally direct chem. activation reaction of neopentyl radical with O2 to form OH (CH3)3CCH2 + O2 → OH + 3,3-dimethyloxetane (Rxn 1) At 673 K and 60 Torr, log k1 (cm3 mol.-1 s-1) = -13.7 ± 0.5. Abs. absorbance measurements on OH and I indicate that the branching ratio for R + O2 to OH is about 0.03 under these conditions. The data suggest that the ab initio neopentyl + O2 potential energy surface of Sun and Bozzelli is accurate to within 2 kcal mol-1.
- 101Hansen, N.; Merchant, S. S.; Harper, M. R.; Green, W. H. The Predictive Capability of an Automatically Generated Combustion Chemistry Mechanism: Chemical Structures of Premixed Iso-Butanol Flames. Combust. Flame 2013, 160, 2343– 2351, DOI: 10.1016/j.combustflame.2013.05.013101https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXpsV2ksbY%253D&md5=e7e16e09c9c3b50328ce0686d91b3b37The predictive capability of an automatically generated combustion chemistry mechanism: Chemical structures of premixed iso-butanol flamesHansen, Nils; Merchant, Shamel S.; Harper, Michael R.; Green, William H.Combustion and Flame (2013), 160 (11), 2343-2351CODEN: CBFMAO; ISSN:0010-2180. (Elsevier B.V.)The chem. compns. of four low-pressure premixed flames of iso-butanol are investigated with an emphasis on assessing the predictive capabilities of an automatically generated combustion chem. model. This kinetic model had been extensively tested against earlier exptl. data [S.S. Merchant, E.F. Zanoelo, R.L. Speth, M.R. Harper, K.M. Van Geem, W.H. Green, Combust. Flame (2013), http://dx.doi.org/10.1016/j.combustflame.2013.04.023.] and also shows impressive capabilities for predicting the new flame data presented here. The new set of data consists of isomer-resolved mole fraction profiles for more than 40 species in each of the four flames and provides a comprehensive benchmark for testing of any combustion chem. model for iso-butanol. Isomer-specificity is achieved by analyzing flames, which are burner-stabilized at equivalence ratios of .vphi. = 1.0-1.5 and at pressures between 15-30 Torr, with mol.-beam mass spectrometry and single-photon ionization by tunable vacuum-UV synchrotron radiation. Predictions of the C2H4O, C3H6O, and C4H8O enol-aldehyde-ketone isomers are improved compared to the earlier work by Hansen et al. [N. Hansen, M. R. Harper, W. H. Green, Phys. Chem. Chem. Phys. 13 (2011) 20262-20274] on similar n-butanol flames. A reaction path anal. identifies prominent fuel-consumption and oxidn. sequences. Almost all of the species mole fraction data reported here are predicted within the measurement uncertainties of a factor of two to three. Some significant differences with previous published models are highlighted.
- 102Slakman, B. L.; Simka, H.; Reddy, H.; West, R. H. Extending Reaction Mechanism Generator to Silicon Hydride Chemistry. Ind. Eng. Chem. Res. 2016, 55, 12507– 12515, DOI: 10.1021/acs.iecr.6b02402102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslOhsr%252FI&md5=51d944ea4978704bfbe0e0f68e7e0ca0Extending Reaction Mechanism Generator to Silicon Hydride ChemistrySlakman, Belinda L.; Simka, Harsono; Reddy, Harinath; West, Richard H.Industrial & Engineering Chemistry Research (2016), 55 (49), 12507-12515CODEN: IECRED; ISSN:0888-5885. (American Chemical Society)Understanding the gas-phase chem. of Si hydrides is the 1st step to building a realistic kinetic model for chem. vapor deposition (CVD). Functionality for thermodn. and kinetic data estn. of Si hydrides was added to the open-source software Reaction Mechanism Generator (RMG). Using the updated RMG, a detailed kinetic model was built for SiH4 thermal decompn. The generated model was used to perform reactor simulations at various process conditions for comparison to prior SiH4 decompn. expts. in a flow tube. Results show that the RMG-generated model can reasonably replicate exptl. results for SiH4 concn. profiles at different temps. and residence times. While the effect of changing initial SiH4 concn. is not captured, a 1st pass sensitivity anal. reveals that reasonable errors in reaction rates could contribute to the discrepancy.
- 103Seyedzadeh Khanshan, F.; West, R. H. Developing Detailed Kinetic Models of Syngas Production from Bio-Oil Gasification Using Reaction Mechanism Generator (RMG). Fuel 2016, 163, 25– 33, DOI: 10.1016/j.fuel.2015.09.031103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFersbjJ&md5=40a7d6183fcf086f287431148682cde2Developing detailed kinetic models of syngas production from bio-oil gasification using Reaction Mechanism Generator (RMG)Seyedzadeh Khanshan, Fariba; West, Richard H.Fuel (2016), 163 (), 25-33CODEN: FUELAC; ISSN:0016-2361. (Elsevier Ltd.)Detailed kinetic models for the conversion of bio-oil to syngas through gasification were developed automatically using the open source software package Reaction Mechanism Generator (RMG). The influences of process operating conditions and of RMG parameters on the performance of models were investigated. Both temp. and pressure alter the product yields, although including pressure-dependent (chem. activated and fall-off) kinetics have minimal impact on these predictions. The model size is important, although currently constrained by available RAM, motivating development of improved memory-management algorithms in RMG. To validate the RMG-built mechanisms, simulations performed with Cantera were compared with exptl. data from the literature. Agreements and disagreements between RMG-built models and literature show that the automated mechanism generation approach is promising, but reveal some families of reactions involving heteroat. cycles that require improved ests. for bio-mass derived fuels. Research in this area would be greatly helped by more quant. exptl. data, ideally showing intermediate species profiles. These findings motivate extra studies and guide further RMG development.
- 104Han, K.; Green, W. H.; West, R. H. On-the-Fly Pruning for Rate-Based Reaction Mechanism Generation. Comput. Chem. Eng. 2017, 100, 1– 8, DOI: 10.1016/j.compchemeng.2017.01.003104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXisVGgtLw%253D&md5=b48df5ab6c5e4d5f93447f5a562f8270On-the-fly pruning for rate-based reaction mechanism generationHan, Kehang; Green, William H.; West, Richard H.Computers & Chemical Engineering (2017), 100 (), 1-8CODEN: CCENDW; ISSN:0098-1354. (Elsevier B.V.)The no. of possible side reactions and byproduct species grows very rapidly with the size of a chem. mechanism. A memory-efficient algorithm for automated mechanism generation is presented for coping with this combinatorial complexity. The algorithm selects normalized flux as a metric to identify unimportant species during model generation and prunes them with their reactions, without any loss of accuracy. The new algorithm reduces memory requirements for building kinetic models with 200-300 species by about a factor of 4, or for fixed computer hardware makes it possible to create models including about twice as many species as was previously possible. The increased capability opens the possibility of discovering unexplored reaction networks and modeling more complicated reacting systems.
- 105Dana, A. G.; Buesser, B.; Merchant, S. S.; Green, W. H. Automated Reaction Mechanism Generation Including Nitrogen as a Heteroatom. Int. J. Chem. Kinet. 2018, 50, 243– 258, DOI: 10.1002/kin.21154105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVOqtbo%253D&md5=5ce0d70f40dea1ec2bea8cfac28998b0Automated Reaction Mechanism Generation Including Nitrogen as a HeteroatomDana, Alon Grinberg; Buesser, Beat; Merchant, Shamel S.; Green, William H.International Journal of Chemical Kinetics (2018), 50 (4), 243-258CODEN: IJCKBO; ISSN:0538-8066. (John Wiley & Sons, Inc.)The open source rate-based Reaction Mechanism Generator (RMG) software and its thermochem. and kinetics databases were extended to include nitrogen as a heteroatom. Specific changes to RMG and the mining of thermochem. and reaction kinetics data are discussed. This new version of RMG has been tested by generating a detailed pyrolysis and oxidn. model for ethylamine (EA, CH3CH2NH2) at ∼1400 K and ∼2 bar, and comparing it to recent shock tube studies. Validation of the reaction network with recent exptl. data showed that the generated model successfully reproduced the obsd. species as well as ignition delay measurements. During pyrolysis, EA initially decomps. via a C-C bond scission, and the CH2NH2 product subsequently produces the first H radicals in this system via β-scission. As the concn. of H increases, the major EA consuming reaction becomes H abstraction at the α-site by H radicals, leading to a chain reaction since its product generates more H radicals. During oxidn., the dominant N2-producing route is mediated by NO and N2O. The observables were found to be relatively sensitive to the C-C and C-N EA bond scission reactions as well as to the thermodn. values of EA; thermodn. data for EA were computed at the CBS-QB3 level and reported herein. This work demonstrates the ability of RMG to construct adequate kinetic models for nitrogenous species and discusses the pyrolysis and oxidn. mechanisms of EA.
- 106Grambow, C. A.; Jamal, A.; Li, Y.-P.; Green, W. H.; Zádor, J.; Suleimanov, Y. V. Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery Methods. J. Am. Chem. Soc. 2018, 140, 1035– 1048, DOI: 10.1021/jacs.7b11009106https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitVaksr%252FN&md5=cc0ce7340d7035db8729dd9cc71478d5Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery MethodsGrambow, Colin A.; Jamal, Adeel; Li, Yi-Pei; Green, William H.; Zador, Judit; Suleimanov, Yury V.Journal of the American Chemical Society (2018), 140 (3), 1035-1048CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Ketohydroperoxides are important in liq.-phase autoxidn. and in gas-phase partial oxidn. and pre-ignition chem., but because of their low concn., instability, and various anal. chem. limitations, it has been challenging to exptl. det. their reactivity, and only a few pathways are known. In the present work, 75 elementary-step unimol. reactions of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, were discovered by a combination of d. functional theory with several automated transition-state search algorithms: the Berny algorithm coupled with the freezing string method, single- and double-ended growing string methods, the heuristic KinBot algorithm, and the single-component artificial force induced reaction method (SC-AFIR). The present joint approach significantly outperforms previous manual and automated transition-state searches - 68 of the reactions of γ-ketohydroperoxide discovered here were previously unknown and completely unexpected. All of the methods found the lowest-energy transition state, which corresponds to the first step of the Korcek mechanism, but each algorithm except for SC-AFIR detected several reactions not found by any of the other methods. We show that the low-barrier chem. reactions involve promising new chem. that may be relevant in atm. and combustion systems. Our study highlights the complexity of chem. space exploration and the advantage of combined application of several approaches. Overall, the present work demonstrates both the power and the weaknesses of existing fully automated approaches for reaction discovery which suggest possible directions for further method development and assessment in order to enable reliable discovery of all important reactions of any specified reactant(s).
- 107Suleimanov, Y. V.; Green, W. H. Automated Discovery of Elementary Chemical Reaction Steps Using Freezing String and Berny Optimization Methods. J. Chem. Theory Comput. 2015, 11, 4248, DOI: 10.1021/acs.jctc.5b00407107https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1Srsb7I&md5=d430c76d756be29d6c52befc113e6400Automated Discovery of Elementary Chemical Reaction Steps Using Freezing String and Berny Optimization MethodsSuleimanov, Yury V.; Green, William H.Journal of Chemical Theory and Computation (2015), 11 (9), 4248-4259CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We present a simple protocol which allows fully automated discovery of elementary chem. reaction steps using in cooperation double- and single-ended transition-state optimization algorithms - the freezing string and Berny optimization methods, resp. To demonstrate the utility of the proposed approach, the reactivity of several single-mol. systems of combustion and atm. chem. importance is investigated. The proposed algorithm allowed us to detect without any human intervention not only "known" reaction pathways, manually detected in the previous studies, but also new, previously "unknown", reaction pathways which involve significant atom rearrangements. We believe that applying such a systematic approach to elementary reaction path finding will greatly accelerate the discovery of new chem. and will lead to more accurate computer simulations of various chem. processes.
- 108Schlegel, H. B. Optimization of Equilibrium Geometries and Transition Structures. J. Comput. Chem. 1982, 3, 214– 218, DOI: 10.1002/jcc.540030212108https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL38XktFajtrY%253D&md5=81448fcccb0620eff4b6754171e84f70Optimization of equilibrium geometries and transition structuresSchlegel, H. BernhardJournal of Computational Chemistry (1982), 3 (2), 214-18CODEN: JCCHDD; ISSN:0192-8651.A modified conjugate gradient algorithm for geometry optimization is outlined for use with ab initio MO methods. Since the computation time for anal. energy gradients is approx. the same as for the energy, the optimization algorithm evaluates and utilizes the gradients each time the energy is computed. The second deriv. matrix, rather than its inverse, is updated employing the gradients. At each step, a one-dimensional minimization using a quartic polynomial is carried out, followed by an n-dimensional search using the second deriv. matrix. By suitably controlling the no. of neg. eigenvalues of the second deriv. matrix, the algorithm can also be used to locate transition structures. Representative timeing data for optimizations of equil. geometries and transition structures are reported for ab initio SCF-MO calcns.
- 110Peng, C.; Ayala, P. Y.; Schlegel, H. B.; Frisch, M. J. Using Redundant Internal Coordinates to Optimize Equilibrium Geometries and Transition States. J. Comput. Chem. 1996, 17, 49– 56, DOI: 10.1002/(SICI)1096-987X(19960115)17:1<49::AID-JCC5>3.0.CO;2-0110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XpvFSi&md5=330450a8e3f31abc94db9435cfe23935Using redundant internal coordinates to optimize equilibrium geometries and transition statesPeng, Chunyang; Ayala, Philippe; Schlegel, H. Bernhard; Frisch, Michael J.Journal of Computational Chemistry (1996), 17 (1), 49-56CODEN: JCCHDD; ISSN:0192-8651. (Wiley)A redundant internal coordinate system for optimizing mol. geometries is constructed from all bonds, all valence angles between bonded atoms, and all dihedral angles between bonded atoms. Redundancies are removed by using the generalized inverse of the G matrix; constraints can be added by using an appropriate projects. For minimizations, redundant internal coordinates provide substantial improvements in optimization efficiency over Cartesian and nonredundant internal coordinates, esp. for flexible and polycyclic systems. Transition structure searches are also improved when redundant coordinates are used and when the initial steps are guided by the quadratic synchronous transit approach.
- 111Bhoorasingh, P. L.; West, R. H. Transition State Geometry Prediction Using Molecular Group Contributions. Phys. Chem. Chem. Phys. 2015, 17, 32173– 32182, DOI: 10.1039/C5CP04706D111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFKhtb3P&md5=16e7f411e54e0417dfd07bbf66ac66b2Transition state geometry prediction using molecular group contributionsBhoorasingh, Pierre L.; West, Richard H.Physical Chemistry Chemical Physics (2015), 17 (48), 32173-32182CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Detailed kinetic models to aid the understanding of complex chem. systems require many thousands of reaction rate coeffs., most of which are estd., some quite approx. and with unknown uncertainties. This motivates the development of high-throughput methods to det. rate coeffs. via transition state theory calcns., which requires the automatic prediction of transition state (TS) geometries. We demonstrate a novel approach to predict TS geometries using a group-additive method. Distances between reactive atoms at the TS are estd. using mol. group values, with the 3D geometry of the TS being constructed by distance geometry. The est. is then optimized using electronic structure theory and validated using intrinsic reaction coordinate calcns., completing the fully automatic algorithm to locate TS geometries. The methods were tested using a diisopropyl ketone combustion model contg. 1393 hydrogen abstraction reactions, of which transition states were found for 907 over two iterations of the algorithm. With sufficient training data, mol. group contributions were shown to successfully predict the reaction center distances of transition states with root-mean-squared errors of only 0.04 Å.
- 112Rappoport, D.; Galvin, C. J.; Zubarev, D. Y.; Aspuru-Guzik, A. Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry. J. Chem. Theory Comput. 2014, 10, 897– 907, DOI: 10.1021/ct401004r112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVOqurY%253D&md5=64f81a54964e1e07a08421b61e45f495Complex Chemical Reaction Networks from Heuristics-Aided Quantum ChemistryRappoport, Dmitrij; Galvin, Cooper J.; Zubarev, Dmitry Yu.; Aspuru-Guzik, AlanJournal of Chemical Theory and Computation (2014), 10 (3), 897-907CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)While structures and reactivities of many small mols. can be computed efficiently and accurately using quantum chem. methods, heuristic approaches remain essential for modeling complex structures and large-scale chem. systems. Here, we present a heuristics-aided quantum chem. methodol. applicable to complex chem. reaction networks such as those arising in cell metab. and prebiotic chem. Chem. heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chem. structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chem. methodol. to the formose reaction reproduces the exptl. obsd. reaction products, major reaction pathways, and autocatalytic cycles.
- 113Zubarev, D. Y.; Rappoport, D.; Aspuru-Guzik, A. Uncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid Cycle. Sci. Rep. 2015, 5, 8009, DOI: 10.1038/srep08009113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXotlagsrs%253D&md5=76b8b2e61796a6a68b76dd84a9e3b45dUncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid CycleZubarev, Dmitry Yu; Rappoport, Dmitrij; Aspuru-Guzik, AlanScientific Reports (2015), 5 (), 8009/1-8009/7CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)We consider the hypothesis of the primordial nature of the non-enzymic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chem. transformations. Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.
- 116Levy, D. E. Arrow-Pushing in Organic Chemistry: An Easy Approach to Understanding Reaction Mechanisms, 2nd ed.; Wiley, 2017.There is no corresponding record for this reference.
- 117Kim, Y.; Woo Kim, J.; Kim, Z.; Youn Kim, W. Efficient Prediction of Reaction Paths through Molecular Graph and Reaction Network Analysis. Chem. Sci. 2018, 9, 825– 835, DOI: 10.1039/C7SC03628K117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFGnsbjI&md5=71d81e16d0ac1ee7164da8f664e8dcbbEfficient prediction of reaction paths through molecular graph and reaction network analysisKim, Yeonjoon; Kim, Jin Woo; Kim, Zeehyo; Kim, Woo YounChemical Science (2018), 9 (4), 825-835CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)Despite remarkable advances in computational chem., prediction of reaction mechanisms is still challenging, because investigating all possible reaction pathways is computationally prohibitive due to the high complexity of chem. space. A feasible strategy for efficient prediction is to utilize chem. heuristics. Here, we propose a novel approach to rapidly search reaction paths in a fully automated fashion by combining chem. theory and heuristics. A key idea of our method is to ext. a minimal reaction network composed of only favorable reaction pathways from the complex chem. space through mol. graph and reaction network anal. This can be done very efficiently by exploring the routes connecting reactants and products with min. dissocn. and formation of bonds. Finally, the resulting minimal network is subjected to quantum chem. calcns. to det. kinetically the most favorable reaction path at the predictable accuracy. As example studies, our method was able to successfully find the accepted mechanisms of Claisen ester condensation and cobalt-catalyzed hydroformylation reactions.
- 118Zimmerman, P. M. Automated Discovery of Chemically Reasonable Elementary Reaction Steps. J. Comput. Chem. 2013, 34, 1385– 1392, DOI: 10.1002/jcc.23271118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXktFWhtb4%253D&md5=443c5c1be4f67d956c120a64a77ee82dAutomated discovery of chemically reasonable elementary reaction stepsZimmerman, Paul M.Journal of Computational Chemistry (2013), 34 (16), 1385-1392CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Due to the significant human effort and chem. intuition required to locate chem. reaction pathways with quantum chem. modeling, only a small subspace of possible reactions is usually studied for any given system. Herein, a systematic approach is proposed for locating reaction paths that bypasses the required human effort and expands the reactive search space, all while maintaining low computational cost. To achieve this, a range of intermediates are generated that represent potential single elementary steps away from a starting structure. These structures are then screened to identify those that are thermodynamically accessible, and then feasible reaction paths to the remaining structures are located. This strategy for elementary reaction path finding is independent of atomistic model whenever bond breaking and forming are properly described. The approach is demonstrated to work well for upper main group elements, but this limitation can easily be surpassed. Further extension will allow discovery of multistep reaction mechanisms in a single computation. The method is highly parallel, allowing for effective use of modern large-scale computational clusters. © 2013 Wiley Periodicals, Inc.
- 119Zimmerman, P. M. Navigating Molecular Space for Reaction Mechanisms: An Efficient, Automated Procedure. Mol. Simul. 2015, 41, 43– 54, DOI: 10.1080/08927022.2014.894999119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltFait7k%253D&md5=4e996b3b2f43c78843468df3e622b79aNavigating molecular space for reaction mechanisms: an efficient, automated procedureZimmerman, Paul M.Molecular Simulation (2015), 41 (1-3), 43-54CODEN: MOSIEA; ISSN:0892-7022. (Taylor & Francis Ltd.)A review; mechanism is a core chem. concept that has vital implications for reaction rate, efficiency and selectivity. The discovery of mechanism is not easy due to the great diversity of possible chem. rearrangements in even relatively simple systems. For this reason, mechanisms involving bond breaking and forming are usually proposed via chem. intuition - which limits the scope of considered possibilities - and these hypotheses are then tested using simulation or expt. This article discusses an automated simulation strategy for investigating multiple elementary step reaction mechanisms in chem. systems. The method starts from a single input structure and seeks out nearby intermediates, optimizes the proposed structures and then dets. the kinetic viability of each elementary step. The kinetically accessible intermediates are catalogued and new searches are performed on each unique structure. This process is repeated for an arbitrary no. of steps without human intervention, and massively parallel computation enables fast searches in chem. space. Importantly, this strategy can be empirically shown to lead to a finite no. of accessible structures, not a combinatorial explosion of intermediates. Therefore, the method should be able to predict multi-step reaction pathways in many interesting chem. systems. Demonstrations on org. reactions and a hydrogen storage material, ammonia borane, show that the herein proposed strategy can uncover complex reactivity without relying on existing chem. intuition.
- 120Zimmerman, P. M. Growing String Method with Interpolation and Optimization in Internal Coordinates: Method and Examples. J. Chem. Phys. 2013, 138, 184102, DOI: 10.1063/1.4804162120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsV2isLg%253D&md5=e315e6f2a3e4e1bf65e743d1ee3863b5Growing string method with interpolation and optimization in internal coordinates: Method and examplesZimmerman, Paul M.Journal of Chemical Physics (2013), 138 (18), 184102/1-184102/10CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The growing string method (GSM) has proven esp. useful for locating chem. reaction paths at low computational cost. While many string methods use Cartesian coordinates, these methods can be substantially improved by changes in the coordinate system used for interpolation and optimization steps. The quality of the interpolation scheme is esp. important because it dets. how close the initial path is to the optimized reaction path, and this strongly affects the rate of convergence. In this article, a detailed description of the generation of internal coordinates (ICs) suitable for use in GSM as reactive tangents and in string optimization is given. Convergence of reaction paths is smooth because the IC tangent and orthogonal directions are better representations of chem. bonding compared to Cartesian coordinates. This is not only important quant. for reducing computational cost but also allows reaction paths to be described with smoothly varying chem. relevant coordinates. Benchmark computations with challenging reactions are compared to previous versions of GSM and show significant speedups. Finally, a climbing image scheme is included to improve the quality of the transition state approxn., ensuring high reliability of the method. (c) 2013 American Institute of Physics.
- 121Zimmerman, P. M. Single-Ended Transition State Finding with the Growing String Method. J. Comput. Chem. 2015, 36, 601– 611, DOI: 10.1002/jcc.23833121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXltVKlsQ%253D%253D&md5=4b3087ccfd79ea3fba13820a2be013e3Single-ended transition state finding with the growing string methodZimmerman, Paul M.Journal of Computational Chemistry (2015), 36 (9), 601-611CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Reaction path finding and transition state (TS) searching are important tasks in computational chem. Methods that seek to optimize an evenly distributed set of structures to represent a chem. reaction path are known as double-ended string methods. Such methods can be highly reliable because the endpoints of the string are fixed, which effectively lowers the dimensionality of the reaction path search. String methods, however, require that the reactant and product structures are known beforehand, which limits their ability for systematic exploration of reactive steps. In this article, a single-ended growing string method (GSM) is introduced which allows for reaction path searches starting from a single structure. The method works by sequentially adding nodes along coordinates that drive bonds, angles, and/or torsions to a desired reactive outcome. After the string is grown and an approx. reaction path through the TS is found, string optimization commences and the exact TS is located along with the reaction path. Fast convergence of the string is achieved through use of internal coordinates and eigenvector optimization schemes combined with Hessian ests. Comparison to the double-ended GSM shows that single-ended method can be even more computationally efficient than the already rapid double-ended method. Examples, including transition metal reactivity and a systematic, automated search for unknown reactivity, demonstrate the efficacy of the new method. This automated reaction search is able to find 165 reaction paths from 333 searches for the reaction of NH3BH3 and (LiH)4, all without guidance from user intuition. © 2015 Wiley Periodicals, Inc.
- 122Jafari, M.; Zimmerman, P. M. Reliable and Efficient Reaction Path and Transition State Finding for Surface Reactions with the Growing String Method. J. Comput. Chem. 2017, 38, 645– 658, DOI: 10.1002/jcc.24720122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslSju74%253D&md5=a8441a251705eefd13a4c844ad88da74Reliable and efficient reaction path and transition state finding for surface reactions with the growing string methodJafari, Mina; Zimmerman, Paul M.Journal of Computational Chemistry (2017), 38 (10), 645-658CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)The computational challenge of fast and reliable transition state and reaction path optimization requires new methodol. strategies to maintain low cost, high accuracy, and systematic searching capabilities. The growing string method using internal coordinates has proven to be highly effective for the study of mol., gas phase reactions, but difficulties in choosing a suitable coordinate system for periodic systems has prevented its use for surface chem. New developments are therefore needed, and presented herein, to handle surface reactions which include atoms with large coordination nos. that cannot be treated using std. internal coordinates. The double-ended and single-ended growing string methods are implemented using a hybrid coordinate system, then benchmarked for a test set of 43 elementary reactions occurring on surfaces. These results show that the growing string method is at least 45% faster than the widely used climbing image-nudged elastic band method, which also fails to converge in several of the test cases. Addnl., the surface growing string method has a unique single-ended search method which can move outward from an initial structure to find the intermediates, transition states, and reaction paths simultaneously. This powerful explorative feature of single ended-growing string method is demonstrated to uncover, for the first time, the mechanism for at. layer deposition of TiN on Cu(111) surface. This reaction is found to proceed through multiple hydrogen-transfer and ligand-exchange events, while formation of H-bonds stabilizes intermediates of the reaction. Purging gaseous products out of the reaction environment is the driving force for these reactions. © 2017 Wiley Periodicals, Inc.
- 123Nett, A. J.; Zhao, W.; Zimmerman, P. M.; Montgomery, J. Highly Active Nickel Catalysts for C–H Functionalization Identified through Analysis of Off-Cycle Intermediates. J. Am. Chem. Soc. 2015, 137, 7636– 7639, DOI: 10.1021/jacs.5b04548123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVansLzJ&md5=a505b5a761d3a525a26dbb20f9b815e9Highly Active Nickel Catalysts for C-H Functionalization Identified through Analysis of Off-Cycle IntermediatesNett, Alex J.; Zhao, Wanxiang; Zimmerman, Paul M.; Montgomery, JohnJournal of the American Chemical Society (2015), 137 (24), 7636-7639CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)An inhibitory role of 1,5-cyclooctadiene (COD) in nickel-catalyzed C-H functionalization processes was identified and studied. The bound COD participates in C-H activation by capturing the hydride, leading to a stable off-cycle π-allyl complex that greatly diminished overall catalytic efficiency. Computational studies elucidated the origin of the effect and enabled identification of a 1,5-hexadiene-derived pre-catalyst that avoids the off-cycle intermediate and provides catalytic efficiencies that are superior to those of catalysts derived from Ni(COD)2.
- 125Pendleton, I. M.; Pérez-Temprano, M. H.; Sanford, M. S.; Zimmerman, P. M. Experimental and Computational Assessment of Reactivity and Mechanism in C(sp3)–N Bond-Forming Reductive Elimination from Palladium(IV). J. Am. Chem. Soc. 2016, 138, 6049– 6060, DOI: 10.1021/jacs.6b02714125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmtF2murk%253D&md5=f739ebd816c70d6b9930b82153ca7aa7Experimental and Computational Assessment of Reactivity and Mechanism in C(sp3)-N Bond-Forming Reductive Elimination from Palladium(IV)Pendleton, Ian M.; Perez-Temprano, Monica H.; Sanford, Melanie S.; Zimmerman, Paul M.Journal of the American Chemical Society (2016), 138 (18), 6049-6060CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)This report describes a combined exptl. and computational investigation of the mechanism of C(sp3)-N bond-forming reductive elimination from sulfonamide-ligated PdIV complexes. After an initial exptl. assessment of reactivity, we used ZStruct, a computational combinatorial reaction finding method, to analyze a large no. of multistep mechanisms for this process. This study reveals two facile isomerization pathways connecting the exptl. obsd. PdIV isomers, along with two competing SN2 pathways for C(sp3)-N coupling. One of these pathways involves an unanticipated oxygen-nitrogen exchange of the sulfonamide ligand prior to an inner-sphere SN2-type reductive elimination. The calcd. ΔG⧺ values for isomerization and reductive elimination with a series of sulfonamide derivs. are in good agreement with exptl. data. Furthermore, the simulations predict relative reaction rates with different sulfonamides, which is successful only after considering competition between the proposed operating mechanisms. Overall, this work shows that the combination of exptl. studies and new computational tools can provide fundamental mechanistic insights into complex organometallic reaction pathways.
- 126Zhao, Y.; Nett, A. J.; McNeil, A. J.; Zimmerman, P. M. Computational Mechanism for Initiation and Growth of Poly(3-Hexylthiophene) Using Palladium N-Heterocyclic Carbene Precatalysts. Macromolecules 2016, 49, 7632– 7641, DOI: 10.1021/acs.macromol.6b01648There is no corresponding record for this reference.
- 127Dewyer, A. L.; Zimmerman, P. M. Finding Reaction Mechanisms, Intuitive or Otherwise. Org. Biomol. Chem. 2017, 15, 501– 504, DOI: 10.1039/C6OB02183B127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVyjtbjJ&md5=1f70486f3755a036f7a878bbf98bc52bFinding reaction mechanisms, intuitive or otherwiseDewyer, Amanda L.; Zimmerman, Paul M.Organic & Biomolecular Chemistry (2017), 15 (3), 501-504CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)Chem. reaction mechanisms have been frequently studied using computational simulations, but these tools have been primarily effective at examg. reaction paths within the scope of chem. intuition. To det. reaction mechanisms that were not already preconceived by chemists, nonstandard simulation tools are required. This perspective introduces new methods developed by the Zimmerman group that are designed to uncover sequences of elementary steps, from first principles and without substantial human guidance. Results from the areas of organo catalysis and transition metal catalysis indicate that new frontiers of knowledge will be gained through continued development and application of reaction discovery simulation techniques.
- 128Ludwig, J. R.; Zimmerman, P. M.; Gianino, J. B.; Schindler, C. S. Iron(III)-Catalysed Carbonyl–Olefin Metathesis. Nature 2016, 533, 374– 379, DOI: 10.1038/nature17432128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmvVGntrY%253D&md5=4763c79022c8121eef0dc857214954dbIron(III)-catalysed carbonyl-olefin metathesisLudwig, Jacob R.; Zimmerman, Paul M.; Gianino, Joseph B.; Schindler, Corinna S.Nature (London, United Kingdom) (2016), 533 (7603), 374-379CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)The olefin metathesis reaction of two unsatd. substrates is one of the most powerful carbon-carbon-bond-forming reactions in org. chem. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of mols. relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.
- 129Smith, M. L.; Leone, A. K.; Zimmerman, P. M.; McNeil, A. J. Impact of Preferential π-Binding in Catalyst-Transfer Polycondensation of Thiazole Derivatives. ACS Macro Lett. 2016, 5, 1411– 1415, DOI: 10.1021/acsmacrolett.6b00886129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVejsLbP&md5=ecff32183eb4d751c490869b57211ab3Impact of Preferential π-Binding in Catalyst-Transfer Polycondensation of Thiazole DerivativesSmith, Mitchell L.; Leone, Amanda K.; Zimmerman, Paul M.; McNeil, Anne J.ACS Macro Letters (2016), 5 (12), 1411-1415CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)Polymg. electron-deficient arenes in a controlled, chain-growth fashion remains a significant challenge despite a decade of research on catalyst-transfer polycondensation. The prevailing hypothesis is that the chain-growth mechanism stalls at a strongly assocd. metal-polymer π-complex, preventing catalyst turnover. To evaluate this hypothesis, we performed mechanistic studies using thiazole derivs. and identified approaches to improve their chain-growth polymn. These studies revealed a surprisingly high barrier for chain-walking toward the reactive C-X bond. In addn., a competitive pathway involving chain-transfer to monomer was identified. This pathway is facilitated by ancillary ligand dissocn. and N-coordination to the incoming monomer. We found that this chain-transfer pathway can be attenuated by using a rigid ancillary ligand, leading to an improved polymn. Combined, these studies provide mechanistic insight into the challenges assocd. with electron-deficient monomers and ways to improve their living, chain-growth polymn. Our mechanistic studies also revealed an unexpected radical anion-mediated oligomerization in the absence of catalyst, and a surprising oxidative addn. into the thiazole C-S bond in a model system.
- 130Ludwig, J. R.; Phan, S.; McAtee, C. C.; Zimmerman, P. M.; Devery, J. J.; Schindler, C. S. Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis Reaction. J. Am. Chem. Soc. 2017, 139, 10832– 10842, DOI: 10.1021/jacs.7b05641130https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1egt7jM&md5=4a6fef8b15abcdf907ae50c6cfda4874Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis ReactionLudwig, Jacob R.; Phan, Susan; McAtee, Christopher C.; Zimmerman, Paul M.; Devery, James J., III; Schindler, Corinna S.Journal of the American Chemical Society (2017), 139 (31), 10832-10842CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Iron(III)-catalyzed carbonyl-olefin ring-closing metathesis represents a new approach toward the assembly of mols. traditionally generated by olefin-olefin metathesis or olefination. Herein, we report detailed synthetic, spectroscopic, kinetic, and computational studies to det. the mechanistic features imparted by iron(III), substrate, and temp. to the catalytic cycle. These data are consistent with an iron(III)-mediated asynchronous, concerted [2+2]-cycloaddn. to form an intermediate oxetane as the turnover-limiting step. Fragmentation of the oxetane via Lewis acid-activation results in the formation of five- and six-membered unsatd. carbocycles.
- 131Dewyer, A. L.; Zimmerman, P. M. Simulated Mechanism for Palladium-Catalyzed, Directed γ-Arylation of Piperidine. ACS Catal. 2017, 7, 5466– 5477, DOI: 10.1021/acscatal.7b01390131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1SjtrrL&md5=6411ffbbfdd8b838027c426c5c1ca207Simulated Mechanism for Palladium-Catalyzed, Directed γ-Arylation of PiperidineDewyer, Amanda L.; Zimmerman, Paul M.ACS Catalysis (2017), 7 (8), 5466-5477CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Quantum chem. reaction path finding methods are herein used to investigate the mechanism of Pd-catalyzed distal functionalization of piperidine, as reported by Sanford. These methods allowed navigation of a complex reaction landscape with multiple reactants interacting at all key steps of the proposed catalytic cycle. A multistep cycle is shown to conceptually begin with substrate ligation and Pd(II)-catalyzed C-H activation, which occurs through concerted metalation-deprotonation. In subsequent steps, the kinetic and thermodn. profiles for oxidative addn., reductive elimination, and catalyst regeneration show why excess Cs salts and ArI were required in the expt. Specifically, excess ArI is necessary to thermodynamically overcome the high energy of the C-H activated intermediate and allow oxidative addn. to be favorable, and excess Cs salt is needed to sequester reaction byproducts during oxidative addn. and catalyst regeneration. The overall catalytic profile is consistent with rate-limiting C-H activation, explains the probable functions of all major exptl. conditions, and gives atomistic detail to guide expt. to improve this challenging transformation even further.
- 132Habershon, S. Sampling Reactive Pathways with Random Walks in Chemical Space: Applications to Molecular Dissociation and Catalysis. J. Chem. Phys. 2015, 143, 094106, DOI: 10.1063/1.4929992132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVCms73P&md5=10d9945d033f6fcbdf91a9a4859d4243Sampling reactive pathways with random walks in chemical space: Applications to molecular dissociation and catalysisHabershon, ScottJournal of Chemical Physics (2015), 143 (9), 094106/1-094106/14CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Automatically generating chem. reaction pathways is a significant computational challenge, particularly in the case where a given chem. system can exhibit multiple reactants and products, as well as multiple pathways connecting these. Here, we outline a computational approach to allow automated sampling of chem. reaction pathways, including sampling of different chem. species at the reaction end-points. The key features of this scheme are (i) introduction of a Hamiltonian which describes a reaction "string" connecting reactant and products, (ii) definition of reactant and product species as chem. connectivity graphs, and (iii) development of a scheme for updating the chem. graphs assocd. with the reaction end-points. By performing mol. dynamics sampling of the Hamiltonian describing the complete reaction pathway, we are able to sample multiple different paths in configuration space between given chem. products; by periodically modifying the connectivity graphs describing the chem. identities of the end-points we are also able to sample the allowed chem. space of the system. Overall, this scheme therefore provides a route to automated generation of a "roadmap" describing chem. reactivity. This approach is first applied to model dissocn. pathways in formaldehyde, H2CO, as described by a parameterised potential energy surface (PES). A second application to the HCo(CO)3 catalyzed hydroformylation of ethene (oxo process), using d. functional tight-binding to model the PES, demonstrates that our graph-based approach is capable of sampling the intermediate paths in the commonly accepted catalytic mechanism, as well as several secondary reactions. Further algorithmic improvements are suggested which will pave the way for treating complex multi-step reaction processes in a more efficient manner. (c) 2015 American Institute of Physics.
- 133Habershon, S. Automated Prediction of Catalytic Mechanism and Rate Law Using Graph-Based Reaction Path Sampling. J. Chem. Theory Comput. 2016, 12, 1786– 1798, DOI: 10.1021/acs.jctc.6b00005133https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xjs1Sqtbk%253D&md5=f227bc5d2e1be8e62e71c72bf772bb71Automated Prediction of Catalytic Mechanism and Rate Law Using Graph-Based Reaction Path SamplingHabershon, ScottJournal of Chemical Theory and Computation (2016), 12 (4), 1786-1798CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)In a recent article [ J. Chem. Phys. 2015, 143, 094106], we introduced a novel graph-based sampling scheme which can be used to generate chem. reaction paths in many-atom systems in an efficient and highly automated manner. The main goal of this work is to demonstrate how this approach, when combined with direct kinetic modeling, can be used to det. the mechanism and phenomenol. rate law of a complex catalytic cycle, namely cobalt-catalyzed hydroformylation of ethene. Our graph-based sampling scheme generates 31 unique chem. products and 32 unique chem. reaction pathways; these sampled structures and reaction paths enable automated construction of a kinetic network model of the catalytic system when combined with d. functional theory (DFT) calcns. of free energies and resultant transition-state theory rate consts. Direct simulations of this kinetic network across a range of initial reactant concns. enables detn. of both the reaction mechanism and the assocd. rate law in an automated fashion, without the need for either presupposing a mechanism or making steady-state approxns. in kinetic anal. Most importantly, we find that the reaction mechanism which emerges from these simulations is exactly that originally proposed by Heck and Breslow; furthermore, the simulated rate law is also consistent with previous exptl. and computational studies, exhibiting a complex dependence on carbon monoxide pressure. While the inherent errors of using DFT simulations to model chem. reactivity limit the quant. accuracy of our calcd. rates, this work confirms that our automated simulation strategy enables direct anal. of catalytic mechanisms from first principles.
- 134Wheeler, S. E.; Seguin, T. J.; Guan, Y.; Doney, A. C. Noncovalent Interactions in Organocatalysis and the Prospect of Computational Catalyst Design. Acc. Chem. Res. 2016, 49, 1061– 1069, DOI: 10.1021/acs.accounts.6b00096134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmsFCrsLw%253D&md5=4cffcbf91f93ae4ecaf20537c364fcebNoncovalent Interactions in Organocatalysis and the Prospect of Computational Catalyst DesignWheeler, Steven E.; Seguin, Trevor J.; Guan, Yanfei; Doney, Analise C.Accounts of Chemical Research (2016), 49 (5), 1061-1069CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Noncovalent interactions are ubiquitous in org. systems, and can play decisive roles in the outcome of asym. organocatalytic reactions. Their prevalence, combined with the often subtle line sepg. favorable dispersion interactions from unfavorable steric interactions, often complicates the identification of the particular noncovalent interactions responsible for stereoselectivity. Ultimately, the stereoselectivity of most organocatalytic reactions hinges on the balance of both favorable and unfavorable noncovalent interactions in the stereocontrolling transition state (TS). In this Account, we provide an overview of our attempts to understand the role of noncovalent interactions in organocatalyzed reactions and to develop new computational tools for organocatalyst design. Following a brief discussion of noncovalent interactions involving arom. rings and the assocd. challenges capturing these effects computationally, we summarize two examples of chiral phosphoric acid catalyzed reactions in which noncovalent interactions play pivotal, although somewhat unexpected, roles. In the first, List's catalytic asym. Fischer indole reaction, we show that both π-stacking and CH/π interactions of the substrate with the 3,3'-aryl groups of the catalyst impact the stability of the stereocontrolling TS. However, these noncovalent interactions oppose each other, with π-stacking interactions stabilizing the TS leading to one enantiomer and CH/π interactions preferentially stabilizing the competing TS. Ultimately, the CH/π interactions dominate and, when combined with hydrogen bonding interactions, lead to preferential formation of the obsd. product. In the second example, a series of phosphoric acid catalyzed asym. ring openings of meso-epoxides, we show that noncovalent interactions of the substrates with the 3,3'-aryl groups of the catalyst play only an indirect role in stereoselectivity. Instead, the stereoselectivity of these reactions are driven by the electrostatic stabilization of a fleeting partial pos. charge in the SN2-like transition state by the chiral electrostatic environment of the phosphoric acid catalyst. Next, we describe our studies of bipyridine N-oxide and N,N'-dioxide catalyzed alkylation reactions. Based on several examples, we demonstrate that there are many potential arrangements of ligands around a hexacoordinate silicon in the stereocontrolling TS, and one must consider all of these in order to identify the lowest-lying TS structures. We also present a model in which electrostatic interactions between a formyl CH group and a chlorine in these TSs underlie the enantioselectivity of these reactions. Finally, we discuss our efforts to develop computational tools for the screening of potential organocatalyst designs, starting in the context of bipyridine N,N'-dioxide catalyzed alkylation reactions. Our new computational tool kit (AARON) has been used to design highly effective catalysts for the asym. propargylation of benzaldehyde, and is currently being used to screen catalysts for other reactions. We conclude with our views on the potential roles of computational chem. in the future of organocatalyst design.
- 135Doney, A. C.; Rooks, B. J.; Lu, T.; Wheeler, S. E. Design of Organocatalysts for Asymmetric Propargylations through Computational Screening. ACS Catal. 2016, 6, 7948– 7955, DOI: 10.1021/acscatal.6b02366135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1yks7jO&md5=207d00d90bba03b6dfeed14f3762364aDesign of Organocatalysts for Asymmetric Propargylations through Computational ScreeningDoney, Analise C.; Rooks, Benjamin J.; Lu, Tongxiang; Wheeler, Steven E.ACS Catalysis (2016), 6 (11), 7948-7955CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)The development of asym. catalysts is typically driven by the exptl. screening of potential catalyst designs. Herein, the authors demonstrate the design of asym. propargylation catalysts through computational screening. This was done using computational toolkit AARON (automated alkylation reaction optimizer for N-oxides), which automates the prediction of enantioselectivities for bidentate Lewis base catalyzed alkylation reactions. A systematic screening of 59 potential catalysts built on 6 bipyridine N,N'-dioxide-derived scaffolds results in predicted ee values for the propargylation of benzaldehyde ranging from 45% (S) to 99% (R), with 12 ee values exceeding 95%. These data provide a broad set of exptl. testable predictions. Also, the assocd. data revealed key details regarding the role of stabilizing electrostatic interactions in asym. propargylations, which were harnessed in the design of a propargylation catalyst for which the predicted ee exceeds 99%.
- 137Guan, Y.; Ingman, V. M.; Rooks, B. J.; Wheeler, S. E. AARON: An Automated Reaction Optimizer for New Catalysts. J. Chem. Theory Comput. 2018, 14, 5249, DOI: 10.1021/acs.jctc.8b00578137https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVOlsbbO&md5=f8e15c28a5e202415fbb232e93310a79AARON: An Automated Reaction Optimizer for New CatalystsGuan, Yanfei; Ingman, Victoria M.; Rooks, Benjamin J.; Wheeler, Steven E.Journal of Chemical Theory and Computation (2018), 14 (10), 5249-5261CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We describe an open-source computational toolkit (AARON: An Automated Reaction Optimizer for New catalysts) that automates the quantum mech. geometry optimization and characterization of the transition state and intermediate structures required to predict the activities and selectivities of asym. catalytic reactions. Modern computational quantum chem. has emerged as a powerful tool for explaining the selectivity and activity of asym. catalysts. However, reliably predicting the stereochem. outcome of realistic reactions often requires the geometry optimization of hundreds of transition state and intermediate structures, which is a tedious process. AARON automates these optimizations through an interface with a popular electronic structure package, accelerating quantum chem. workflows to enable the computational screening of potential catalysts. AARON is built using a collection of object-oriented Perl modules (AaronTools) that provide functionality to build and modify mol. and supramol. structures. The main functionalities of AaronTools are also available as stand-alone command-line scripts. The core features of AaronTools and AARON are explained, and representative applications of AARON to both organocatalyzed and transition-metal-catalyzed reactions are presented.
- 138Geerlings, P.; De Proft, F.; Langenaeker, W. Conceptual Density Functional Theory. Chem. Rev. 2003, 103, 1793– 1874, DOI: 10.1021/cr990029p138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXivFGgu7g%253D&md5=085c8ae5893c0b05158629e182ecb0a4Conceptual Density Functional TheoryGeerlings, P.; De Proft, F.; Langenaeker, W.Chemical Reviews (Washington, DC, United States) (2003), 103 (5), 1793-1873CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review on conceptual d. functional theory including the following topics: fundamental and computational aspects of DFT, DFT-based concepts and principles and applications of DFT.
- 139Geerlings, P.; Proft, F. D. Conceptual DFT: The Chemical Relevance of Higher Response Functions. Phys. Chem. Chem. Phys. 2008, 10, 3028– 3042, DOI: 10.1039/b717671f139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtVKmt7o%253D&md5=d0abd6b5a14679da7da2cef53918a636Conceptual DFT: the chemical relevance of higher response functionsGeerlings, P.; De Proft, F.Physical Chemistry Chemical Physics (2008), 10 (21), 3028-3042CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)A review. In recent years conceptual d. functional theory offered a perspective for the interpretation/prediction of exptl./theor. reactivity data on the basis of a series of response functions to perturbations in the no. of electrons and/or external potential. This approach has enabled the sharp definition and computation, from first principles, of a series of well-known but sometimes vaguely defined chem. concepts such as electronegativity and hardness. In this contribution, a short overview of the shortcomings of the simplest, first-order response functions is illustrated leading to a description of chem. bonding in a covalent interaction in terms of interacting atoms or groups, governed by electrostatics with the tendency to polarize bonds on the basis of electronegativity differences. The second order approach, well known until now, introduces the hardness/softness and Fukui function concepts related to polarizability and frontier MO theory, resp. The introduction of polarizability/softness is also considered in a historical perspective in which polarizability was, with some exceptions, mainly put forward in non covalent interactions. A particular series of response functions, arising when the changes in the external potential are solely provoked by changes in nuclear configurations (the "R-analogs") are also systematically considered. The main part of the contribution is devoted to third-order response functions which, at first sight, may be expected not to yield chem. significant information, as turns out to be for the hyperhardness. A counterexample is the dual descriptor and its R analog, the initial hardness response, which turns out to yield a firm basis to regain the Woodward-Hoffmann rules for pericyclic reactions based on a d.-only basis, i.e. without involving the phase, sign, symmetry of the wavefunction. Even the second-order nonlinear response functions are shown possibly to bear interesting information, e.g. on the local and global polarizability. Its derivs. may govern the influence of charge on the polarizability, the R-analogs being the nuclear Fukui function and the quadratic and cubic force consts. Although some of the higher order derivs. may be difficult to evaluate a comparison with the energy expansion used in spectroscopy in terms of nuclear displacements, nuclear magnetic moments, elec. and magnetic fields leads to the conjecture that, certainly cross terms may contain new, intricate information for understanding chem. reactivity.
- 141Bergeler, M.; Simm, G. N.; Proppe, J.; Reiher, M. Heuristics-Guided Exploration of Reaction Mechanisms. J. Chem. Theory Comput. 2015, 11, 5712– 5722, DOI: 10.1021/acs.jctc.5b00866141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslCjtbjO&md5=c283427244c99d448f5c895d6f434b06Heuristics-Guided Exploration of Reaction MechanismsBergeler, Maike; Simm, Gregor N.; Proppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2015), 11 (12), 5712-5722CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)For the investigation of chem. reaction networks, the efficient and accurate detn. of all relevant intermediates and elementary reactions is mandatory. The complexity of such a network may grow rapidly, in particular if reactive species are involved that might cause a myriad of side reactions. Without automation, a complete investigation of complex reaction mechanisms is tedious and possibly unfeasible. Therefore, only the expected dominant reaction paths of a chem. reaction network (e.g., a catalytic cycle or an enzymic cascade) are usually explored in practice. Here, we present a computational protocol that constructs such networks in a parallelized and automated manner. Mol. structures of reactive complexes are generated based on heuristic rules derived from conceptual electronic-structure theory and subsequently optimized by quantum-chem. methods to produce stable intermediates of an emerging reaction network. Pairs of intermediates in this network that might be related by an elementary reaction according to some structural similarity measure are then automatically detected and subjected to an automated search for the connecting transition state. The results are visualized as an automatically generated network graph, from which a comprehensive picture of the mechanism of a complex chem. process can be obtained that greatly facilitates the anal. of the whole network. We apply our protocol to the Schrock dinitrogen-fixation catalyst to study alternative pathways of catalytic ammonia prodn.
- 143Yandulov, D. V.; Schrock, R. R. Reduction of Dinitrogen to Ammonia at a Well-Protected Reaction Site in a Molybdenum Triamidoamine Complex. J. Am. Chem. Soc. 2002, 124, 6252– 6253, DOI: 10.1021/ja020186x143https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XjsVyhsb8%253D&md5=5a7abc5e8c8135193ceb83918f21ea43Reduction of Dinitrogen to Ammonia at a Well-Protected Reaction Site in a Molybdenum Triamidoamine ComplexYandulov, Dmitry V.; Schrock, Richard R.Journal of the American Chemical Society (2002), 124 (22), 6252-6253CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We have synthesized a triamidoamine ligand ([(RNCH2CH2)3N]3-) in which R is 3,5-(2,4,6-i-Pr3C6H2)2C6H3 (HexaIsoPropylTerphenyl or HIPT). The reaction between MoCl4(THF)2 and H3[HIPTN3N] in THF followed by 3.1 equiv of LiN(SiMe3)2 led to formation of orange [HIPTN3N]MoCl. Redn. of [HIPTN3N]MoCl with magnesium in THF under dinitrogen led to formation of salts that contain the {[HIPTN3N]Mo(N2)}- ion. The {[HIPTN3N]Mo(N2)}- ion can be oxidized by zinc chloride to give [HIPTN3N]Mo(N2) or protonated to give [HIPTN3N]Mo-N:N-H. Other relevant compds. that have been prepd. include {[HIPTN3N]Mo-N:NH2}+, [HIPTN3N]Mo≡N, {[HIPTN3N]Mo:NH}+, and {[HIPTN3N]Mo(NH3)}+. (The anion is usually {B(3,5-(CF3)2C6H3)4}- = {BAr'4}-.). Redn. of [HIPTN3N]Mo(N2) with CoCp2 in the presence of {2,6-lutidinium}BAr'4 in benzene leads to formation of ammonia and {[HIPTN3N]Mo(NH3)}+. Preliminary X-ray studies suggest that the HIPT substituent creates a deep, three-fold sym. cavity that protects a variety of dinitrogen redn. products against bimol. decompn. reactions, while at the same time the metal is left relatively open toward reactions near the equatorial amido ligands.
- 144Yandulov, D. V.; Schrock, R. R.; Rheingold, A. L.; Ceccarelli, C.; Davis, W. M. Synthesis and Reactions of Molybdenum Triamidoamine Complexes Containing Hexaisopropylterphenyl Substituents. Inorg. Chem. 2003, 42, 796– 813, DOI: 10.1021/ic020505l144https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjt1yqtg%253D%253D&md5=224f2e5ebc46cf53c66ce1e68f6de311Synthesis and Reactions of Molybdenum Triamidoamine Complexes Containing Hexaisopropylterphenyl SubstituentsYandulov, Dmitry V.; Schrock, Richard R.; Rheingold, Arnold L.; Ceccarelli, Christopher; Davis, William M.Inorganic Chemistry (2003), 42 (3), 796-813CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)The authors synthesized a triamidoamine ligand ([(RNCH2CH2)3N]3-) in which R is 3,5-(2,4,6-i-Pr3C6H2)2C6H3 (hexaisopropylterphenyl or HIPT). The reaction between MoCl4(THF)2 and H3[HIPTN3N] in THF followed by 3.1 equiv of LiN(SiMe3)2 gave orange [HIPTN3N]MoCl. Redn. of MoCl (Mo = [HIPTN3N]Mo) with Mg in THF under dinitrogen gave salts that contain the {Mo(N2)}- ion. The {Mo(N2)}- ion can be oxidized by ZnCl2 to give Mo(N2) or protonated to give MoN:NH. The latter decomps. to yield MoH. Other relevant compds. that were prepd. include {Mo:N-NH2}+ (by protonation of MoN:NH), Mo≡N, {Mo=NH}+ (by protonation of Mo≡N), and {Mo(NH3)}+ (by treating MoCl with NH3) (The anion is usually {B(3,5-(CF3)2C6H3)4}- = {BAr'4}-). X-ray studies were carried out on {Mg(DME)3}0.5[Mo(N2)], MoN:NMgBr(THF)3, Mo(N2), Mo≡N, and {Mo(NH3)}{BAr'4}. Probably the HIPT substituent on the triamidoamine ligand creates a cavity that stabilizes a variety of complexes that might be encountered in a hypothetical Chatt-like dinitrogen redn. scheme, perhaps largely by protecting against bimol. decompn. reactions.
- 145Eschenmoser, A.; Loewenthal, E. Chemistry of Potentially Prebiological Natural Products. Chem. Soc. Rev. 1992, 21, 1– 16, DOI: 10.1039/cs9922100001145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38Xht1egtL4%253D&md5=26e2c8a468693ecdbff4a3b01d3766beChemistry of potentially prebiological natural productsEschenmoser, Albert; Loewenthal, EliChemical Society Reviews (1992), 21 (1), 1-16CODEN: CSRVBR; ISSN:0306-0012.A review with 59 refs. on the title subject with regard to sugar phosphates, purines, pyrimidines and oligonucleotides.
- 146Delidovich, I. V.; Simonov, A. N.; Taran, O. P.; Parmon, V. N. Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective Synthesis. ChemSusChem 2014, 7, 1833– 1846, DOI: 10.1002/cssc.201400040146https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpslGjtLw%253D&md5=3f51d7aa82ef147a6e790097a698e7c5Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective SynthesisDelidovich, Irina V.; Simonov, Alexandr N.; Taran, Oxana P.; Parmon, Valentin N.ChemSusChem (2014), 7 (7), 1833-1846CODEN: CHEMIZ; ISSN:1864-5631. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The formose reaction (FR) was long the focus of intensive studies as a simple method for synthesis of complex biol. important monosaccharides and other sugar-like mols. from the simplest org. substrate-formaldehyde. The fundamental importance of the FR is predominantly connected with the ascertainment of plausible scenarios of chem. evolution which could occurred on the prebiotic Earth to produce the very first mols. of carbohydrates, amino- and nucleic acids, as well as other vitally important substances. The practical importance of studies on the FR is the elaboration of catalytic methods for the synthesis of rare and nonnatural monosaccharides and polyols. This Minireview considers the FR from the point of view of chemists working in the field of catalysis with emphasis on the mechanisms of numerous parallel and consequent catalytic transformations that take place during the FR. Based on its kinetics, the FR may be considered as a nonradical chain process with degenerate branching. The Minireview also considers different approaches to the control of selectivity of carbohydrate synthesis from formaldehyde and lower monosaccharides.
- 147Simm, G. N.; Reiher, M. Context-Driven Exploration of Complex Chemical Reaction Networks. J. Chem. Theory Comput. 2017, 13, 6108– 6119, DOI: 10.1021/acs.jctc.7b00945147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsleiurfJ&md5=1a898dab5d04f2c4889afb549a4dbb5aContext-Driven Exploration of Complex Chemical Reaction NetworksSimm, Gregor N.; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (12), 6108-6119CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The construction of a reaction network contg. all relevant intermediates and elementary reactions is necessary for the accurate description of chem. processes. In the case of a complex chem. reaction (involving, for instance, many reactants or highly reactive species), the size of such a network may grow rapidly. Here, we present a computational protocol that constructs such reaction networks in a fully automated fashion steered in an intuitive, graph-based fashion through a single graphical user interface. Starting from a set of initial reagents new intermediates are explored through intra- and intermol. reactions of already explored intermediates or new reactants presented to the network. This is done by assembling reactive complexes based on heuristic rules derived from conceptual electronic-structure theory and exploring the corresponding approx. reaction path. A subsequent path refinement leads to a min.-energy path which connects the new intermediate to the existing ones to form a connected reaction network. Tree traversal algorithms are then employed to detect reaction channels and catalytic cycles. We apply our protocol to the formose reaction to study different pathways of sugar formation and to rationalize its autocatalytic nature.
- 150Husch, T.; Reiher, M. Comprehensive analysis of the neglect of diatomic differential overlap approximation. J. Chem. Theory Comput. 2018, 14, 5169– 5179, DOI: 10.1021/acs.jctc.8b00601150https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1KhtbzI&md5=1410f3e6922bfcc2d97eb12e6ebbb005Comprehensive Analysis of the Neglect of Diatomic Differential Overlap ApproximationHusch, Tamara; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (10), 5169-5179CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Many modern semiempirical MO models are built on the NDDO approxn. An in-depth understanding of this approxn. is therefore indispensable to rationalize the success of these semiempirical MO models and to develop further improvements on them. The NDDO approxn. provides a recipe to approx. electron-electron repulsion integrals (ERIs) in a sym. orthogonalized basis based on a far smaller no. of ERIs in a locally orthogonalized basis. We first analyze the NDDO approxn. by comparing ERIs in both bases for a selection of mols. and for a selection of basis sets. We find that the errors in Hartree-Fock and second-order Moller-Plesset perturbation theory energies grow roughly linearly with the no. of basis functions. We then examine different approaches to correct for the errors caused by the NDDO approxn. and propose a strategy to directly correct for them in the two-electron matrixes that enter the Fock operator.
- 151Simm, G. N.; Proppe, J.; Reiher, M. Error Assessment of Computational Models in Chemistry. Chimia 2017, 71, 202– 208, DOI: 10.2533/chimia.2017.202151https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1ajt7rK&md5=88488125dbc1ae5214a8b22d52d9570bError assessment of computational models in chemistrySimm, Gregor N.; Proppe, Jonny; Reiher, MarkusChimia (2017), 71 (4), 202-208CODEN: CHIMAD ISSN:. (Swiss Chemical Society)Computational models in chem. rely on a no. of approxns. The effect of such approxns. on observables derived from them is often unpredictable. Therefore, it is challenging to quantify the uncertainty of a computational result, which, however, is necessary to assess the suitability of a computational model. Common performance statistics such as the mean abs. error are prone to failure as they do not distinguish the explainable (systematic) part of the errors from their unexplainable (random) part. In this paper, we discuss problems and solns. for performance assessment of computational models based on several examples from the quantum chem. literature. For this purpose, we elucidate the different sources of uncertainty, the elimination of systematic errors, and the combination of individual uncertainty components to the uncertainty of a prediction.
- 152Proppe, J.; Reiher, M. Reliable Estimation of Prediction Uncertainty for Physicochemical Property Models. J. Chem. Theory Comput. 2017, 13, 3297– 3317, DOI: 10.1021/acs.jctc.7b00235152https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXpt1ykt7w%253D&md5=41bb917d7e3707ab9c6308a00dd056c9Reliable Estimation of Prediction Uncertainty for Physicochemical Property ModelsProppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (7), 3297-3317CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)One of the major challenges in computational science is to det. the uncertainty of a virtual measurement, that is the prediction of an observable based on calcns. As highly accurate first-principles calcns. are in general unfeasible for most phys. systems, one usually resorts to parameteric property models of observables, which require calibration by incorporating ref. data. The resulting predictions and their uncertainties are sensitive to systematic errors such as inconsistent ref. data, parametric model assumptions, or inadequate computational methods. Here, we discuss the calibration of property models in the light of bootstrapping, a sampling method that can be employed for identifying systematic errors and for reliable estn. of the prediction uncertainty. We apply bootstrapping to assess a linear property model linking the 57Fe Mossbauer isomer shift to the contact electron d. at the iron nucleus for a diverse set of 44 mol. iron compds. The contact electron d. is calcd. with 12 d. functionals across Jacob's ladder (PWLDA, BP86, BLYP, PW91, PBE, M06-L, TPSS, B3LYP, B3PW91, PBE0, M06, TPSSh). We provide systematic-error diagnostics and reliable, locally resolved uncertainties for isomer-shift predictions. Pure and hybrid d. functionals yield av. prediction uncertainties of 0.06-0.08 mm s-1 and 0.04-0.05 mm s-1, resp., the latter being close to the av. exptl. uncertainty of 0.02 mm s-1. Furthermore, we show that both model parameters and prediction uncertainty depend significantly on the compn. and no. of ref. data points. Accordingly, we suggest that rankings of d. functionals based on performance measures (e.g., the squared coeff. of correlation, r2, or the root-mean-square error, RMSE) should not be inferred from a single data set. This study presents the first statistically rigorous calibration anal. for theor. Mossbauer spectroscopy, which is of general applicability for physicochem. property models and not restricted to isomer-shift predictions. We provide the statistically meaningful ref. data set MIS39 and a new calibration of the isomer shift based on the PBE0 functional.
- 153Weymuth, T.; Proppe, J.; Reiher, M. Statistical Analysis of Semiclassical Dispersion Corrections. J. Chem. Theory Comput. 2018, 14, 2480– 2494, DOI: 10.1021/acs.jctc.8b00078153https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmvVaqsL4%253D&md5=723d9ba5398927668bdedd0141a9b508Statistical Analysis of Semiclassical Dispersion CorrectionsWeymuth, Thomas; Proppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (5), 2480-2494CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Semiclassical dispersion corrections developed by Grimme and co-workers have become indispensable in applications of Kohn-Sham d. functional theory. A deeper understanding of the underlying parametrization might be crucial for well-founded further improvements of this successful approach. To this end, we present an in-depth assessment of the fit parameters present in semiclassical (D3-type) dispersion corrections by means of a statistically rigorous anal. We find that the choice of the cost function generally has a small effect on the empirical parameters of D3-type dispersion corrections with respect to the ref. set under consideration. Only in a few cases, the choice of cost function has a surprisingly large effect on the total dispersion energies. In particular, the weighting scheme in the cost function can significantly affect the reliability of predictions. In order to obtain unbiased (data-independent) uncertainty ests. for both the empirical fit parameters and the corresponding predictions, we carried out a nonparametric bootstrap anal. This anal. reveals that the std. deviation of the mean of the empirical D3 parameters is small. Moreover, the mean prediction uncertainty obtained by bootstrapping is not much larger than previously reported error measures. On the basis of a jackknife anal., we find that the original ref. set is slightly skewed, but our results also suggest that this feature hardly affects the prediction of dispersion energies. Furthermore, we find that the introduction of small uncertainties to the ref. data does not change the conclusions drawn in this work. However, a rigorous anal. of error accumulation arising from different parametrizations reveals that error cancellation does not necessarily occur, leading to a monotonically increasing deviation in the dispersion energy with increasing mol. size. We discuss this issue in detail at the prominent example of the C60 "buckycatcher". We find deviations between individual parametrizations of several tens of kilocalories per mol in some cases. Hence, in combination with any calcn. of dispersion energies, we recommend to always det. the assocd. uncertainties for which we will provide a software tool.
- 154Proppe, J.; Husch, T.; Simm, G. N.; Reiher, M. Uncertainty quantification for quantum chemical models of complex reaction networks. Faraday Discuss. 2016, 195, 497– 520, DOI: 10.1039/C6FD00144K154https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFantbbF&md5=72ef620f8bd4517eb0c2c46fa32a05afUncertainty quantification for quantum chemical models of complex reaction networksProppe, Jonny; Husch, Tamara; Simm, Gregor N.; Reiher, MarkusFaraday Discussions (2016), 195 (Reaction Rate Theory), 497-520CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)A review. For the quant. understanding of complex chem. reaction mechanisms, it is, in general, necessary to accurately det. the corresponding free energy surface and to solve the resulting continuous-time reaction rate equations for a continuous state space. For a general (complex) reaction network, it is computationally hard to fulfill these two requirements. However, it is possible to approx. address these challenges in a phys. consistent way. On the one hand, it may be sufficient to consider approx. free energies if a reliable uncertainty measure can be provided. On the other hand, a highly resolved time evolution may not be necessary to still det. quant. fluxes in a reaction network if one is interested in specific time scales. In this paper, we present discrete-time kinetic simulations in discrete state space taking free energy uncertainties into account. The method builds upon thermo-chem. data obtained from electronic structure calcns. in a condensed-phase model. Our kinetic approach supports the anal. of general reaction networks spanning multiple time scales, which is here demonstrated for the example of the formose reaction. An important application of our approach is the detection of regions in a reaction network which require further investigation, given the uncertainties introduced by both approx. electronic structure methods and kinetic models. Such cases can then be studied in greater detail with more sophisticated first-principles calcns. and kinetic simulations.
- 155Simm, G.; Reiher, M. Error-Controlled Exploration of Chemical Reaction Networks with Gaussian Processes. J. Chem. Theory Comput. 2018, 14, 5238– 5248, DOI: 10.1021/acs.jctc.8b00504155https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1Gmt7vK&md5=116ed9b1481210ec5564eb6e1d0157f8Error-Controlled Exploration of Chemical Reaction Networks with Gaussian ProcessesSimm, Gregor N.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (10), 5238-5248CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)For a theor. understanding of the reactivity of complex chem. systems, relative energies of stationary points on potential energy hypersurfaces need to be calcd. to high accuracy. Due to the large no. of intermediates present in all but the simplest chem. processes, approx. quantum chem. methods are required that allow for fast evaluations of the relative energies but at the expense of accuracy. Despite the plethora of benchmark studies, the accuracy of a quantum chem. method is often difficult to assess. Moreover, a significant improvement of a method's accuracy (e.g., through reparameterization or systematic model extension) is rarely possible. Here, we present a new approach that allows for the systematic, problem-oriented, and rolling improvement of quantum chem. results through the application of Gaussian processes. Due to its Bayesian nature, reliable error ests. are provided for each prediction. A ref. method of high accuracy can be employed if the uncertainty assocd. with a particular calcn. is above a given threshold. The new data point is then added to a growing data set in order to continuously improve the model and, as a result, all subsequent predictions. Previous predictions are validated by the updated model to ensure that uncertainties remain within the given confidence bound, which we call backtracking. We demonstrate our approach with the example of a complex chem. reaction network.
- 156Lagorce, D.; Pencheva, T.; Villoutreix, B. O.; Miteva, M. A. DG-AMMOS: A New Tool to Generate 3D Conformation of Small Molecules Using Distance Geometry and Automated Molecular Mechanics Optimization for in Silico Screening. BMC Chem. Biol. 2009, 9, 6, DOI: 10.1186/1472-6769-9-6156https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjnsVKrtA%253D%253D&md5=6722e659d6b334955fbc5239df28e37fDG-AMMOS: a new tool to generate 3d conformation of small molecules using distance geometry and automated molecular mechanics optimization for in silico screeningLagorce David; Villoutreix Bruno O; Miteva Maria A; Pencheva TaniaBMC chemical biology (2009), 9 (), 6 ISSN:.BACKGROUND: Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. RESULTS: Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. CONCLUSION: DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.
- 157Riniker, S.; Landrum, G. A. Better Informed Distance Geometry: Using What We Know To Improve Conformation Generation. J. Chem. Inf. Model. 2015, 55, 2562– 2574, DOI: 10.1021/acs.jcim.5b00654157https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVeqsrjP&md5=8ee6d7d1999924fc2b42f76577f8ec51Better Informed Distance Geometry: Using What We Know To Improve Conformation GenerationRiniker, Sereina; Landrum, Gregory A.Journal of Chemical Information and Modeling (2015), 55 (12), 2562-2574CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Small org. mols. are often flexible, i.e., they can adopt a variety of low-energy conformations in soln. that exist in equil. with each other. Two main search strategies are used to generate representative conformational ensembles for mols.: systematic and stochastic. In the first approach, each rotatable bond is sampled systematically in discrete intervals, limiting its use to mols. with a small no. of rotatable bonds. Stochastic methods, however, sample the conformational space of a mol. randomly and can thus be applied to more flexible mols. Different methods employ different degrees of exptl. data for conformer generation. So-called knowledge-based methods use predefined libraries of torsional angles and ring conformations. In the distance geometry approach, however, a smaller amt. of empirical information was used, i.e., ideal bond lengths, ideal bond angles, and a few ideal torsional angles. Distance geometry is a computationally fast method to generate conformers, but it has the downside that purely distance-based constraints tend to lead to distorted arom. rings and sp2 centers. To correct this, the resulting conformations are often minimized with a force field, adding computational complexity and run time. Here the authors present an alternative strategy that combines the distance geometry approach with exptl. torsion-angle preferences obtained from small-mol. crystallog. data. The torsional angles are described by a previously developed set of hierarchically structured SMARTS patterns. The new approach is implemented in the open-source cheminformatics library RDKit, and its performance is assessed by comparing the diversity of the generated ensemble and the ability to reproduce crystal conformations taken from the crystal structures of small mols. and protein-ligand complexes.
- 158Vainio, M. J.; Johnson, M. S. Generating Conformer Ensembles Using a Multiobjective Genetic Algorithm. J. Chem. Inf. Model. 2007, 47, 2462– 2474, DOI: 10.1021/ci6005646158https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtVOnsL7L&md5=e621e6eedf3d93ff6236bc4887f25e35Generating Conformer Ensembles Using a Multiobjective Genetic AlgorithmVainio, Mikko J.; Johnson, Mark S.Journal of Chemical Information and Modeling (2007), 47 (6), 2462-2474CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The task of generating a nonredundant set of low-energy conformations for small mols. is of fundamental importance for many mol. modeling and drug-design methodologies. Several approaches to conformer generation have been published. Exhaustive searches suffer from the exponential growth of the search space with increasing degrees of conformational freedom (no. of rotatable bonds). Stochastic algorithms do not suffer as much from the exponential increase of search space and provide a good coverage of the energy min. Here, the use of a multiobjective genetic algorithm in the generation of conformer ensembles is investigated. Distance geometry is used to generate an initial conformer, which is then subject to geometric modifications encoded by the individuals of the genetic algorithm. The geometric modifications apply to torsion angles about rotatable bonds, stereochem. of double bonds and tetrahedral chiral centers, and ring conformations. The geometric diversity of the evolving conformer ensemble is preserved by a fitness-sharing mechanism based on the root-mean-square distance of the at. coordinates. Mol. symmetry is taken into account in the distance calcn. The geometric modifications introduce strain into the structures. The strain is relaxed using an MMFF94-like force field in a postprocessing step that also removes conformational duplicates and structures whose strain energy remains above a predefined window from the min. energy value found in the set. The implementation, called Balloon, is available free of charge on the Internet (http://www.abo.fi/∼mivainio/balloon/).
- 160Miteva, M. A.; Guyon, F.; Tufféry, P. Frog2: Efficient 3D Conformation Ensemble Generator for Small Compounds. Nucleic Acids Res. 2010, 38, W622– W627, DOI: 10.1093/nar/gkq325160https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXotVSqsr8%253D&md5=ec1c9860de9eb1e81e9e8d81f24f550bFrog2: Efficient 3D conformation ensemble generator for small compoundsMiteva, Maria A.; Guyon, Frederic; Tuffery, PierreNucleic Acids Research (2010), 38 (Web Server), W622-W627CODEN: NARHAD; ISSN:0305-1048. (Oxford University Press)Frog is a web tool dedicated to small compd. 3D generation. Here we present the new version, Frog2, which allows the generation of conformation ensembles of small mols. starting from either 1D, 2D or 3D description of the compds. From a compd. description in one of the SMILES, SDF or mol2 formats, the server will return an ensemble of diverse conformers generated using a two stage Monte Carlo approach in the dihedral space. When starting from 1D or 2D description of compds., Frog2 is capable to detect the sites of ambiguous stereoisomery, and thus to sample different stereoisomers. Frog2 also embeds new energy minimization and ring generation facilities that solve the problem of some missing cycle structures in the Frog1 ring library. Finally, the optimized generator of conformation ensembles in Frog2 results in a gain of computational time permitting Frog2 to be up to 20 times faster that Frog1, while producing satisfactory conformations in terms of structural quality and conformational diversity. The high speed and the good quality of generated conformational ensembles makes it possible the treatment of larger compd. collections using Frog2. The server and documentation are freely available at http://bioserv.rpbs.univ-paris-diderot.fr/Frog2.
- 161Hawkins, P. C. D.; Skillman, A. G.; Warren, G. L.; Ellingson, B. A.; Stahl, M. T. Conformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural Database. J. Chem. Inf. Model. 2010, 50, 572– 584, DOI: 10.1021/ci100031x161https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjtlaisrY%253D&md5=fb87ecc9c51eddef63b41fffcd9babeeConformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural DatabaseHawkins, Paul C. D.; Skillman, A. Geoffrey; Warren, Gregory L.; Ellingson, Benjamin A.; Stahl, Matthew T.Journal of Chemical Information and Modeling (2010), 50 (4), 572-584CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Here, we present the algorithm and validation for OMEGA, a systematic, knowledge-based conformer generator. The algorithm consists of three phases: assembly of an initial 3D structure from a library of fragments; exhaustive enumeration of all rotatable torsions using values drawn from a knowledge-based list of angles, thereby generating a large set of conformations; and sampling of this set by geometric and energy criteria. Validation of conformer generators like OMEGA has often been undertaken by comparing computed conformer sets to exptl. mol. conformations from crystallog., usually from the Protein Databank (PDB). Such an approach is fraught with difficulty due to the systematic problems with small mol. structures in the PDB. Methods are presented to identify a diverse set of small mol. structures from cocomplexes in the PDB that has maximal reliability. A challenging set of 197 high quality, carefully selected ligand structures from well-solved models was obtained using these methods. This set will provide a sound basis for comparison and validation of conformer generators in the future. Validation results from this set are compared to the results using structures of a set of druglike mols. extd. from the Cambridge Structural Database (CSD). OMEGA is found to perform very well in reproducing the crystallog. conformations from both these data sets using two complementary metrics of success.
- 162Schärfer, C.; Schulz-Gasch, T.; Hert, J.; Heinzerling, L.; Schulz, B.; Inhester, T.; Stahl, M.; Rarey, M. CONFECT: Conformations from an Expert Collection of Torsion Patterns. ChemMedChem 2013, 8, 1690– 1700, DOI: 10.1002/cmdc.201300242162https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3sfotVymtA%253D%253D&md5=9aed22ca5ec1872aea505dadb9d99baeCONFECT: conformations from an expert collection of torsion patternsScharfer Christin; Schulz-Gasch Tanja; Hert Jerome; Heinzerling Lennart; Schulz Benjamin; Inhester Therese; Stahl Martin; Rarey MatthiasChemMedChem (2013), 8 (10), 1690-700 ISSN:.The generation of sets of low-energy conformations for a given molecule is a central task in drug design. Herein we present a new conformation generator called CONFECT that builds on our previously published library of torsion patterns. Conformations are generated as well as ranked by means of normalized frequency distributions derived from the Cambridge Structural Database (CSD). Following an incremental construction approach, conformations are selected from a systematic enumeration within energetic boundaries. The new tool is benchmarked in several different ways, indicating that it allows the efficient generation of high-quality conformation ensembles. These ensembles are smaller than those produced by state-of-the-art tools, yet they effectively cover conformational space.
- 163Guba, W.; Meyder, A.; Rarey, M.; Hert, J. Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small Molecules. J. Chem. Inf. Model. 2016, 56, 1– 5, DOI: 10.1021/acs.jcim.5b00522163https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XovFKjsA%253D%253D&md5=0e26d363bad3069851a04bf977027f53Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small MoleculesGuba, Wolfgang; Meyder, Agnes; Rarey, Matthias; Hert, JeromeJournal of Chemical Information and Modeling (2016), 56 (1), 1-5CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The Torsion Library contains hundreds of rules for small mol. conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by mol. design experts. The torsion rules are encoded as SMARTS patterns and categorize rotatable bonds via a traffic light coloring scheme. We have systematically revised all torsion rules to better identify highly strained conformations and minimize the no. of false alerts for CSD small mol. X-ray structures. For this new release, we added or substantially modified 78 torsion patterns and reviewed all angles and tolerance intervals. The overall no. of red alerts for a filtered CSD data set with 130 000 structures was reduced by a factor of 4 compared to the predecessor. This is of clear advantage in 3D virtual screening where hits should only be removed by a conformational filter if they are in energetically inaccessible conformations.
- 164Batter, J.; Brooks, F. GROPE-I: A Computer Display to the Sense of Feel. Proceedings of the International Federation of Information Processing 1971, 759– 763There is no corresponding record for this reference.
- 165Noll, A. M. Man-Machine Tactile Communication. J. Soc. Inform. Dis. 1972, 6–11, 30There is no corresponding record for this reference.
- 167Lancaster, S. J. Immersed in virtual molecules. Nature Rev. Chem. 2018, 2, 253– 254, DOI: 10.1038/s41570-018-0043-5167https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvVKnsb3M&md5=886aaa061e23d04e29d0b2bdc99df026Immersed in virtual moleculesLancaster, Simon J.Nature Reviews Chemistry (2018), 2 (10), 253-254CODEN: NRCAF7; ISSN:2397-3358. (Nature Research)A full grasp of chem. requires students to be able to connect microscopic reality with symbolic representations. Immersive virtual reality provides a soln. for those who need a tangible link between these representations.
- 168Aspuru-Guzik, A.; Lindh, R.; Reiher, M. The Matter (R)evolution. ACS Cent. Sci. 2018, 4, 144– 152, DOI: 10.1021/acscentsci.7b00550168https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitF2gsrk%253D&md5=b606a11b4272d62ae4f7de4b7709d25aThe Matter Simulation (R)evolutionAspuru-Guzik, Alan; Lindh, Roland; Reiher, MarkusACS Central Science (2018), 4 (2), 144-152CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)To date, the program for the development of methods and models for atomistic and continuum simulation directed toward chems. and materials has reached an incredible degree of sophistication and maturity. Currently, one can witness an increasingly rapid emergence of advances in computing, artificial intelligence, and robotics. This drives us to consider the future of computer simulation of matter from the mol. to the human length and time scales in a radical way that deliberately dares to go beyond the foreseeable next steps in any given discipline. This perspective article presents a view on this future development that we believe is likely to become a reality during our lifetime.
- 170Cruz-Neira, C.; Sandin, D. J.; DeFanti, T. A. Surround-Screen Projection-Based Virtual Reality: The Design and Implementation of the CAVE. Proceedings of the 20th Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, NY, USA, 1993; pp 135– 142.There is no corresponding record for this reference.
- 178Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Comparing Position and Force Control for Interactive Molecular Simulators with Haptic Feedback. J. Mol. Graphics Modell. 2010, 29, 280– 289, DOI: 10.1016/j.jmgm.2010.06.003178https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtFamtLvP&md5=8d81e29d4693725c0ada3ce7db0cebc0Comparing position and force control for interactive molecular simulators with haptic feedbackBolopion, Aude; Cagneau, Barthelemy; Redon, Stephane; Regnier, StephaneJournal of Molecular Graphics & Modelling (2010), 29 (2), 280-289CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)This paper presents a novel tool for the anal. of new mol. structures which enables a wide variety of manipulations. It is composed of a mol. simulator and a haptic device. The simulation software deals with systems of hundreds or thousands of degrees of freedom and computes the reconfiguration of the mols. in a few tenths of a second. For the ease of manipulation and to help the operator understand nanoscale phenomena, a haptic device is connected to the simulator. To handle a wide variety of applications, both position and force control are implemented. To our knowledge, this is the first time the applications of force control are detailed for mol. simulation. These two control modes are compared in terms of adequacy with mol. dynamics, transparency and stability sensitivity with respect to environmental conditions. Based on their specificity the operations they can realize are detailed. Expts. highlight the usability of our tool for the different steps of the anal. of mol. structures. It includes the global reconfiguration of a mol. system, the measurement of mol. properties and the comprehension of nanoscale interactions. Compared to most existing systems, the one developed in this paper offers a wide range of possible expts. The detailed anal. of the properties of the control modes can be easily used to implement haptic feedback on other mol. simulators.
- 181Durlach, N.; Mavor, A.; Development, C.; Board, C.; Council, N. Virtual Reality: Scientific and Technological Challenges; National Academies Press, 1994.There is no corresponding record for this reference.
- 182Mark, W. R.; Randolph, S. C.; Finch, M.; Van Verth, J. M.; Taylor, R. M., II. Adding Force Feedback to Graphics Systems: Issues and Solutions. Proceedings of the 23rd Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, 1996; pp 447– 452.There is no corresponding record for this reference.
- 184Cruz-Neira, C.; Langley, R.; Bash, P. VIBE: A Virtual Biomolecular Environment for Interactive Molecular Modeling. Comput. Chem. 1996, 20, 469– 477, DOI: 10.1016/0097-8485(96)00009-5184https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XlslWhu7Y%253D&md5=c1c2ca7665c30f7500d6b2e721dc29e0VIBE: a virtual biomolecular environment for interactive molecular modelingCruz-Neira, C.; Langley, R.; Bash, P. A.Computers & Chemistry (Oxford) (1996), 20 (4), 469-477CODEN: COCHDK; ISSN:0097-8485. (Elsevier)Virtual reality tightly coupled to high performance computing and communications ushers in a new era for the study of mol. recognition and the rational design of pharmaceutical compds. We have created a Virtual Biomol. Environment (VIBE), which consists of (1) massively parallel computing to simulate the phys. and chem. properties of a mol. system, (2) the Cave Automatic Virtual Environment (CAVE) for immersive display and interaction with the mol. system, and (3) a high-speed network interface to exchange data between the simulation and the CAVE. VIBE enables mol. scientists to have a visual, auditory, and haptic experience with a chem. system, while simultaneously manipulating its phys. properties by steering, in real-time, a simulation executed on a supercomputer. We demonstrate the characteristics of VIBE using a HIV protease-cyclic urea inhibitor complex.
- 185Férey, N.; Nelson, J.; Martin, C.; Picinali, L.; Bouyer, G.; Tek, A.; Bourdot, P.; Burkhardt, J.; Katz, B.; Ammi, M.; Etchebest, C.; Autin, L. Multisensory VR Interaction for Protein-Docking in the CoRSAIRe Project. Virtual Reality 2009, 13, 273– 293, DOI: 10.1007/s10055-009-0136-zThere is no corresponding record for this reference.
- 186Glowacki, D. R.; O’Connor, M.; Calabro, G.; Price, J.; Tew, P.; Mitchell, T.; Hyde, J.; Tew, D. P.; Coughtrie, D. J.; McIntosh-Smith, S. A GPU-Accelerated Immersive Audio-Visual Framework for Interaction with Molecular Dynamics Using Consumer Depth Sensors. Faraday Discuss. 2014, 169, 63– 87, DOI: 10.1039/C4FD00008KThere is no corresponding record for this reference.
- 187Arbon, R. E.; Jones, A. J.; Bratholm, L. A.; Mitchell, T.; Glowacki, D. R. Sonifying Stochastic Walks on Biomolecular Energy Landscapes. 2018, arXiv 1803.05805.There is no corresponding record for this reference.
- 190Levine, D.; Facello, M.; Hallstrom, P.; Reeder, G.; Walenz, B.; Stevens, F. Stalk: An Interactive System for Virtual Molecular Docking. IEEE Comput. Sci. Eng. 1997, 4, 55– 65, DOI: 10.1109/99.609834190https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXkslOksro%253D&md5=13346f7b2c9a5751e55e859fea6dc97dStalk: an interactive system for virtual molecular dockingLevine, David; Facello, Michael; Hallstrom, Philip; Reeder, Gregory; Walenz, Brian; Stevens, FredIEEE Computational Science & Engineering (1997), 4 (2), 55-65CODEN: ISCEE4; ISSN:1070-9924. (IEEE Computer Society)Several recent technols., i.e., genetic algorithms, parallel and distributed computing, virtual reality, and high-speed networking, underlie a new approach to the computational study of how biomols. interact or dock together. With the Stalk system, a user in a virtual reality environment can interact with a genetic algorithm running on a parallel computer to help in the search for likely geometric configurations.
- 192O’Connor, M.; Deeks, H. M.; Dawn, E.; Metatla, O.; Roudaut, A.; Sutton, M.; Thomas, L. M.; Glowacki, B. R.; Sage, R.; Tew, P.; Wonnacott, M.; Bates, P.; Mulholland, A. J.; Glowacki, D. R. Sampling Molecular Conformations and Dynamics in a Multiuser Virtual Reality Framework. Sci. Adv. 2018, 4, eaat2731 DOI: 10.1126/sciadv.aat2731There is no corresponding record for this reference.
- 197Wollacott, A. M.; Merz, K. M., Jr. Haptic Applications for Molecular Structure Manipulation. J. Mol. Graphics Modell. 2007, 25, 801– 805, DOI: 10.1016/j.jmgm.2006.07.005197https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsFOiu7w%253D&md5=53a6dc20d08d1a0de0cee9053589ddf9Haptic applications for molecular structure manipulationWollacott, Andrew M.; Merz, Kenneth M.Journal of Molecular Graphics & Modelling (2007), 25 (6), 801-805CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Inc.)We describe the application of haptic technol. to enhance the information available in chem. systems, specifically related to computational drug design. These methods are designed to build upon the visual information presented by mol. viewers and add the sensation of touch, or force feedback. The addn. of sensory input can aid in the anal. of mol. structures and the understanding of intermol. interactions by delivering chem. relevant forces to the end user.
- 200Anthopoulos, A.; Pasqualetto, G.; Grimstead, I.; Brancale, A. Haptic-Driven, Interactive Drug Design: Implementing a GPU-Based Approach to Evaluate the Induced Fit Effect. Faraday Discuss. 2014, 169, 323– 342, DOI: 10.1039/C3FD00139C200https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7jE&md5=baa69798111ce24fac6a771e906d262eHaptic-driven, interactive drug design: implementing a GPU-based approach to evaluate the induced fit effectAnthopoulos, Athanasios; Pasqualetto, Gaia; Grimstead, Ian; Brancale, AndreaFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 323-342CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)In this paper, we describe a hybrid meta-heuristics method of energy minimization and conformational sampling and its application into our haptic-driven mol. modeling simulator. The proposed method has been designed to suit real-time mol. docking simulations, where the time-lapse between two successive ligand poses is relatively small. In these situations, the energy minimization problem becomes increasingly complex and chaotic. The algorithm is tuned to take advantage of recent advances in GPU computing with asynchronous kernel execution, which has allowed us to include full protein flexibility in the real-time interactive, haptic-driven simulations. Finally, in this paper, we will also discuss the implementation of such high-performance computing approaches in our software, discussing the results of our initial validation studies, highlighting the advantages and limitations of such interactive methodol.
- 201Iakovou, G.; Hayward, S.; Laycock, S. D. A Real-Time Proximity Querying Algorithm for Haptic-Based Molecular Docking. Faraday Discuss. 2014, 169, 359– 377, DOI: 10.1039/C3FD00123G201https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7jP&md5=ba322c73d491c8d3218f2ec2e97f4a3fA real-time proximity querying algorithm for haptic-based molecular dockingIakovou, Georgios; Hayward, Steven; Laycock, StephenFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 359-377CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Intermol. binding underlies every metabolic and regulatory processes of the cell, and the therapeutic and pharmacol. properties of drugs. Mol. docking systems model and simulate these interactions in silico and allow us to study the binding process. Haptic-based docking provides an immersive virtual docking environment where the user can interact with and guide the mols. to their binding pose. Moreover, it allows human perception, intuition and knowledge to assist and accelerate the docking process, and reduces incorrect binding poses. Crucial for interactive docking is the real-time calcn. of interaction forces. For smooth and accurate haptic exploration and manipulation, force-feedback cues have to be updated at a rate of 1 kHz. Hence, force calcns. must be performed within 1ms. To achieve this, modern haptic-based docking approaches often utilize pre-computed force grids and linear interpolation. However, such grids are time-consuming to pre-compute (esp. for large mols.), memory hungry, can induce rough force transitions at cell boundaries and cannot be applied to flexible docking. Here we propose an efficient proximity querying method for computing intermol. forces in real time. Our motivation is the eventual development of a haptic-based docking soln. that can model mol. flexibility. Uniquely in a haptics application we use octrees to decomp. the 3D search space in order to identify the set of interacting atoms within a cut-off distance. Force calcns. are then performed on this set in real time. The implementation constructs the trees dynamically, and computes the interaction forces of large mol. structures (i.e. consisting of thousands of atoms) within haptic refresh rates. We have implemented this method in an immersive, haptic-based, rigid-body, mol. docking application called Haptimol_RD. The user can use the haptic device to orientate the mols. in space, sense the interaction forces on the device, and guide the mols. to their binding pose. Haptimol_RD is designed to run on consumer level hardware, i.e. there is no need for specialized/proprietary hardware.
- 202Iakovou, G.; Hayward, S.; Laycock, S. D. Adaptive GPU-Accelerated Force Calculation for Interactive Rigid Molecular Docking Using Haptics. J. Mol. Graphics Modell. 2015, 61, 1– 12, DOI: 10.1016/j.jmgm.2015.06.003202https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtF2ksbzL&md5=fc7fcb1082a8e50b08323d4ab720b249Adaptive GPU-accelerated force calculation for interactive rigid molecular docking using hapticsIakovou, Georgios; Hayward, Steven; Laycock, Stephen D.Journal of Molecular Graphics & Modelling (2015), 61 (), 1-12CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)Mol. docking systems model and simulate in silico the interactions of intermol. binding. Haptics-assisted docking enables the user to interact with the simulation via their sense of touch, but a stringent time constraint on the computation of forces is imposed due to the sensitivity of the human haptic system. To simulate high fidelity smooth and stable feedback the haptic feedback loop should run at rates of 500 Hz to 1 kHz. The authors present an adaptive force calcn. approach that can be executed in parallel on a wide range of Graphics Processing Units (GPUs) for interactive haptics-assisted docking with wider applicability to mol. simulations. Prior to the interactive session either a regular grid or an octree is selected according to the available GPU memory to det. the set of interat. interactions within a cutoff distance. The total force is then calcd. from this set. The approach can achieve force updates in <2 ms for mol. structures comprising hundreds of thousands of atoms each, with performance improvements of up to 90 times the speed of current CPU-based force calcn. approaches used in interactive docking. Furthermore, it overcomes several computational limitations of previous approaches such as pre-computed force grids, and could potentially be used to model receptor flexibility at haptic refresh rates.
- 203Iakovou, G.; Hayward, S.; Laycock, S. D. Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with Haptics. J. Chem. Inf. Model. 2017, 57, 1142– 1152, DOI: 10.1021/acs.jcim.7b00051203https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmsVahs74%253D&md5=88a043fa234a92e12c81dfd453884b01Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with HapticsIakovou, Georgios; Hayward, Steven; Laycock, Stephen D.Journal of Chemical Information and Modeling (2017), 57 (5), 1142-1152CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Haptic technol. facilitates user interaction with the virtual world via the sense of touch. In mol. docking, haptics enables the user to sense the interaction forces during the docking process. Here the authors describe a haptics-assisted interactive software tool, called Haptimol_RD, for the study of docking interactions. By utilizing GPU-accelerated proximity querying methods very large systems can now be studied. Methods for force scaling, multipoint collision response and haptic navigation are described that address force stability issues that are particular to the interactive docking of large systems. Thus, Haptimol_RD expands, for the first time, the use of interactive biomol. haptics to the study of protein-protein interactions. Unlike existing approaches, Haptimol_RD is designed to run on relatively inexpensive consumer-level hardware and is freely available to the community.
- 204Izrailev, S.; Stepaniants, S.; Isralewitz, B.; Kosztin, D.; Lu, H.; Molnar, F.; Wriggers, W.; Schulten, K. In Computational Molecular Dynamics: Challenges, Methods, Ideas; Deuflhard, P., Hermans, J., Leimkuhler, B., Mark, A., Reich, S., Skeel, R., Eds.; Lecture Notes in Computational Science and Engineering; Springer: Berlin, Heidelberg, 1999; Vol. 4, pp 39– 65.There is no corresponding record for this reference.
- 205Grubmüller, H.; Heymann, B.; Tavan, P. Ligand Binding: Molecular Mechanics Calculation of the Streptavidin-Biotin Rupture Force. Science 1996, 271, 997– 999, DOI: 10.1126/science.271.5251.997205https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XhtFCru7g%253D&md5=8a013b443101d48aed80fcde1ec7d924Ligand binding: molecular mechanics calculation of the streptavidin-biotin rupture forceGrubmueller, Helmut; Heymann, Berthold; Tavan, PaulScience (Washington, D. C.) (1996), 271 (5251), 997-9CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The force required to rupture the streptavidin-biotin complex was calcd. here by computer simulations. The computed force agrees well with that obtained by recent single mol. at. force microscope expts. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, addnl. water bridges substantially enhance the stability of the complex and even dominate the binding interactions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were obsd.
- 206Izrailev, S.; Stepaniants, S.; Balsera, M.; Oono, Y.; Schulten, K. Molecular Dynamics Study of Unbinding of the Avidin-Biotin Complex. Biophys. J. 1997, 72, 1568– 1581, DOI: 10.1016/S0006-3495(97)78804-0206https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXitFeisbk%253D&md5=649ad913ebac2d1b320aebef229a8c50Molecular dynamics study of unbinding of the avidin-biotin complexIzrailev, S.; Stepaniants, S.; Balsera, M.; Oono, Y.; Schulten, K.Biophysical Journal (1997), 72 (4), 1568-1581CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)We report mol. dynamics simulations that induce, over periods of 40-500 ps, the unbinding of biotin from avidin by means of external harmonic forces with force consts. close to those of AFM cantilevers. The applied forces are sufficiently large to reduce the overall binding energy enough to yield unbinding within the measurement time. Our study complements earlier work on biotin-streptavidin that employed a much larger harmonic force const. The simulations reveal a variety of unbinding pathways, the role of key residues contributing to adhesion as well as the spatial range over which avidin binds biotin. In contrast to the previous studies, the calcd. rupture forces exceed by far those obsd. We demonstrate, in the framework of models expressed in terms of one-dimensional Langevin equations with a schematic binding potential, the assocd. Smoluchowski equations, and the theory of first passage times, that picosecond to nanosecond simulation of ligand unbinding requires such strong forces that the resulting protein-ligand motion proceeds far from the thermally activated regime of millisecond AFM expts., and that simulated unbinding cannot be readily extrapolated to the exptl. obsd. rupture.
- 208Isralewitz, B.; Izrailev, S.; Schulten, K. Binding Pathway of Retinal to Bacterio-Opsin: A Prediction by Molecular Dynamics Simulations. Biophys. J. 1997, 73, 2972– 2979, DOI: 10.1016/S0006-3495(97)78326-7208https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXnsl2murc%253D&md5=ad6760df6b7abc856b68c31980e1da86Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulationsIsralewitz, Barry; Izrailev, Sergei; Schulten, KlausBiophysical Journal (1997), 73 (6), 2972-2979CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)Formation of bacteriorhodopsin (bR) from apoprotein and retinal has been studied exptl., but the actual pathway, including the point of entry, is little understood. Mol. dynamics simulations provide a surprisingly clear prediction. A window between bR helixes E and F in the transmembrane part of the protein can be identified as an entry point for retinal. Steered mol. dynamics, performed by applying a series of external forces in the range of 200-1000 pN over a period of 0.2 ns to retinal, allows one to ext. this chromophore from bR once the Schiff base bond to Lys216 is cleaved. Extn. proceeds until the retinal tail forms a hydrogen bond network with the Ala144, Met145, and Ser183 side groups lining the exit/entry window. The manipulation induces a distortion with a fitted root mean square deviation of coordinates (ignoring retinal, water, and hydrogen atoms) of less than 1.9 Å by the time the retinal carbonyl reaches the protein surface. The forces needed to ext. retinal are due to friction and do not indicate significant potential barriers. The simulations therefore suggest a pathway for the binding of retinal. Water mols. are found to play a crucial role in the binding process.
- 209Jarzynski, C. Nonequilibrium Equality for Free Energy Differences. Phys. Rev. Lett. 1997, 78, 2690, DOI: 10.1103/PhysRevLett.78.2690209https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXisVSrt7c%253D&md5=5e572f64b7e9044fff5af96867602877Nonequilibrium equality for free energy differencesJarzynski, C.Physical Review Letters (1997), 78 (14), 2690-2693CODEN: PRLTAO; ISSN:0031-9007. (American Physical Society)An expression is derived for the equil. free energy difference between two configurations of a system, in terms of an ensemble of finite-time measurements of the work performed in parametrically switching from one configuration to the other. Two well-known identities emerge as limiting cases of this result.
- 210Nelson, M.; Humphrey, W.; Kufrin, R.; Gursoy, A.; Dalke, A.; Kale, L.; Skeel, R.; Schulten, K. MDScope — a Visual Computing Environment for Structural Biology. Comput. Phys. Commun. 1995, 91, 111– 133, DOI: 10.1016/0010-4655(95)00045-H210https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXps1Wrtrg%253D&md5=5581371fd83f3a501280347abd691318MDScope - a visual computing environment for structural biologyNelson, Mark; Humphrey, William; Kufrin, Richard; Gursoy, Attila; Dalke, Andrew; Kale, Laxmikant; Skeel, Robert; Schulten, KlausComputer Physics Communications (1995), 91 (1-3), 111-33CODEN: CPHCBZ; ISSN:0010-4655. (Elsevier)MDScope is an integrated set of computational tools which function as an interactive visual computing environment for the simulation and study of biopolymers. This environment consists of three parts: (1) vmd, a mol. visualization program for interactive display of mol. systems; (2) namd, a mol. dynamics program designed for performance, scalability, modularity, and portability, which runs in parallel on a variety of computer platforms; (3) MDComm, a protocol and library which functions as the unifying communication agent between the visualization and simulation components of MDScope. Namd is expressly designed for distributed memory parallel architectures and uses a spatial decompn. parallelization strategy coupled with a multi-threaded, message-driven computation model which reduces inefficiencies due to communication latency. Through the MDComm software, vmd acts as a graphical interface and interactive control for namd, allowing a user running namd to utilize a parallel platform for computational power while visualizing the trajectory as it is computed. Modularity in both vmd and namd is accomplished through an object-oriented design, which facilitates the addn. of features and new algorithms.
- 211Rapaport, D. Interactive Molecular Dynamics. Phys. A 1997, 240, 246– 254, DOI: 10.1016/S0378-4371(97)00148-9211https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXkt1agtLo%253D&md5=8376a0d92a34d61102b994d2dea8e323Interactive molecular dynamicsRapaport, D. C.Physica A: Statistical and Theoretical Physics (Amsterdam) (1997), 240 (1-2), 246-254CODEN: PHYADX; ISSN:0378-4371. (Elsevier)We address the use of visualization and interactivity in mol. dynamics simulation. In an interactive environment the simulator is not only provided with the means to view the system in alternative ways in real-time, but is also able to 'steer' the computation in different directions by changing the governing parameters of the system. The simulational experience can be enhanced significantly by such means. Several examples are outlined.
- 212Rapaport, D. C. An Introduction to Interactive Molecular-Dynamics Simulations. Comput. Phys. 1997, 11, 337– 347, DOI: 10.1063/1.168612212https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmsVCiurs%253D&md5=dd6d05d9bec0be44a4f0deb1ea2828b8An introduction to interactive molecular-dynamics simulationsRapaport, D. C.Computers in Physics (1997), 11 (4), 337-347CODEN: CPHYE2; ISSN:0894-1866. (American Institute of Physics)A review with 8 refs.
- 213Leech, J.; Prins, J. F.; Hermans, J. SMD: Visual Steering of Molecular Dynamics for Protein Design. IEEE Comput. Sci. Eng. 1996, 3, 38– 45, DOI: 10.1109/99.556511213https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXitlSqtQ%253D%253D&md5=6f7100b4048a22f1cdc0a43ab30048b4SMD: visual steering of molecular dynamics for protein designLeech, Jonathan; Prins, Jan F.; Hermans, JanIEEE Computational Science & Engineering (1996), 3 (4), 38-45CODEN: ISCEE4; ISSN:1070-9924. (IEEE Computer Society)SMD, a system for interactively steering mol. dynamics calcns. of protein mols., includes computation, visualization, and communications components. Biochemists can "tug" mols. into different shapes by specifying external forces in the graphical interface, which are added to internal forces representing at. bonds and nonbonded interactions.
- 214Vormoor, O. Quick and Easy Interactive Molecular Dynamics Using Java3D. Comput. Sci. Eng. 2001, 3, 98– 104, DOI: 10.1109/5992.947113214https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFOjt7w%253D&md5=a5b57a2dc0a27f019479fdedba6a44a8Quick and easy interactive molecular dynamics using Java3DVormoor, OliverComputing in Science & Engineering (2001), 3 (5), 98-104CODEN: CSENFA; ISSN:1521-9615. (American Institute of Physics)An interactive mol. dynamics software, called Java Interactive Mol. Dynamics (JIMD), was developed for the study of colloid clusters. JIMD is not a stand-alone interactive mol. dynamic application, but a software package that can be quickly and easily adapted to existing mol. dynamics simulation software. For rendering the mol. system, JIMD uses Java3D, the application programing interface for writing 3D graphics applications in Java.
- 219Dreher, M.; Prevoteau-Jonquet, J.; Trellet, M.; Piuzzi, M.; Baaden, M.; Raffin, B.; Ferey, N.; Robert, S.; Limet, S. ExaViz: A Flexible Framework to Analyse, Steer and Interact with Molecular Dynamics Simulations. Faraday Discuss. 2014, 169, 119– 142, DOI: 10.1039/C3FD00142CThere is no corresponding record for this reference.
- 220Stone, J. E.; Kohlmeyer, A.; Vandivort, K. L.; Schulten, K. In Advances in Visual Computing; Bebis, G., Boyle, R., Parvin, B., Koracin, D., Chung, R., Hammound, R., Hussain, M., Kar-Han, T., Crawfis, R., Thalmann, D., Kao, D., Avila, L., Eds.; Lecture Notes in Computer Science; Springer: Berlin, Heidelberg, 2010; Vol. 6454, pp 382– 393.There is no corresponding record for this reference.
- 221Luehr, N.; Jin, A. G. B.; Martínez, T. J. Ab Initio Interactive Molecular Dynamics on Graphical Processing Units (GPUs). J. Chem. Theory Comput. 2015, 11, 4536– 4544, DOI: 10.1021/acs.jctc.5b00419221https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVeqtrzP&md5=9d5ff51b17633add948dbacc2c22958fAb Initio Interactive Molecular Dynamics on Graphical Processing Units (GPUs)Luehr, Nathan; Jin, Alex G. B.; Martinez, Todd J.Journal of Chemical Theory and Computation (2015), 11 (10), 4536-4544CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)A virtual mol. modeling kit is developed based on GPU-enabled interactive ab initio mol. dynamics (MD). The code uses the TeraChem and VMD programs with a modified IMD interface. Optimization of the GPU accelerated TeraChem program specifically for small mol. systems is discussed, and a robust multiple time step integrator is employed to accurately integrate strong user-supplied pulling forces. Smooth and responsive visualization techniques are developed to allow interactive manipulation at min. simulation rates below five MD steps per s. Representative calcns. at the Hartree-Fock level of theory are demonstrated for mol. systems contg. up to a few dozen atoms.
- 222Surles, M. C.; Richardson, J. S.; Richardson, D. C.; Brooks, F. P. Sculpting Proteins Interactively: Continual Energy Minimization Embedded in a Graphical Modeling System. Protein Sci. 1994, 3, 198– 210, DOI: 10.1002/pro.5560030205222https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXktlSgt74%253D&md5=2138dd23c7212467e7fe17ab717eaa44Sculpting proteins interactively: continual energy minimization embedded in a graphical modeling systemSurles, Mark C.; Richardson, Jane S.; Richardson, David C.; Brooks, Frederick P., Jr.Protein Science (1994), 3 (), 198-210CODEN: PRCIEI; ISSN:0961-8368.The authors describe a new paradigm for modeling proteins in interactive computer graphics systems - continual maintenance of a phys. valid representation, combined with direct user control and visualization. This is achieved by a fast algorithm for energy minimization, capable of real-time performance an all atoms of a small protein, plus graphically specified user tugs. The modeling system, called Sculpt, rigidly constrains bond strengths, bond angles, and planar groups (similar to existing interactive modeling programs), while it applies elastic restraints to minimize the potential energy due to torsions, hydrogen bonds, and van der Waals and electrostatic interactions (similar to existing batch minimization programs), and user-specific springs. The graphical interface can show bad and(or) favorable contacts, and individual energy terms can be turned on or off to det. their effects and interactions. Sculpt finds a local min. of the total energy that satisfies all the constraints using an augmented Lagrange-multiplier method; calcn. time increases only linearly with the no. of atoms because the matrix of constraint gradients is sparse and banded. On a 100-MHz MIPs R4000 processor (Silicon Graphics Indigo), Sculpt achieves 11 updates per s on a 20-residue fragment and 2 updates per s on an 80-residue protein, using all atoms except non-H-bonding hydrogens, and without electrostatic interactions. Applications of Sculpt are described: to reverse the direction of bundle packing in a designed 4-helix bundle protein, to fold up a 2-stranded β-ribbon into an approx. β-barrel, and to design the sequence and conformation of a 30-residue peptide that mimics one partner of a protein subunit interaction. Computer models that are both interactive and phys. realistic (within the limitations of a given force field) have 2 significant advantages: (1) they make feasible the modeling of very large changes (such as needed for de novo design), and (2) they help the user understand how different energy terms interact to stabilize a given conformation. The Sculpt paradigm combines many of the best features of interactive graphical modeling, energy minimization, and actual phys. models, and the authors propose it as an esp. productive way to use current and future increases in computer speed.
- 223Hanwell, M. D.; Curtis, D. E.; Lonie, D. C.; Vandermeersch, T.; Zurek, E.; Hutchison, G. R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminf. 2012, 4, 17, DOI: 10.1186/1758-2946-4-17223https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVGksLg%253D&md5=f10400f51db314afa780e99403ca748aAvogadro: an advanced semantic chemical editor, visualization, and analysis platformHanwell, Marcus D.; Curtis, Donald E.; Lonie, David C.; Vandermeersch, Tim; Zurek, Eva; Hutchison, Geoffrey R.Journal of Cheminformatics (2012), 4 (), 17CODEN: JCOHB3; ISSN:1758-2946. (Chemistry Central Ltd.)Background: The Avogadro project has developed an advanced mol. editor and visualizer designed for cross-platform use in computational chem., mol. modeling, bioinformatics, materials science, and related areas. It offers flexible, high quality rendering, and a powerful plugin architecture. Typical uses include building mol. structures, formatting input files, and analyzing output of a wide variety of computational chem. packages. By using the CML file format as its native document type, Avogadro seeks to enhance the semantic accessibility of chem. data types. Results: The work presented here details the Avogadro library, which is a framework providing a code library and application programming interface (API) with three-dimensional visualization capabilities; and has direct applications to research and education in the fields of chem., physics, materials science, and biol. The Avogadro application provides a rich graphical interface using dynamically loaded plugins through the library itself. The application and library can each be extended by implementing a plugin module in C++ or Python to explore different visualization techniques, build/manipulate mol. structures, and interact with other programs. We describe some example extensions, one which uses a genetic algorithm to find stable crystal structures, and one which interfaces with the PackMol program to create packed, solvated structures for mol. dynamics simulations. The 1.0 release series of Avogadro is the main focus of the results discussed here. Conclusions: Avogadro offers a semantic chem. builder and platform for visualization and anal. For users, it offers an easy-to-use builder, integrated support for downloading from common databases such as PubChem and the Protein Data Bank, extg. chem. data from a wide variety of formats, including computational chem. output, and native, semantic support for the CML file format. For developers, it can be easily extended via a powerful plugin mechanism to support new features in org. chem., inorg. complexes, drug design, materials, biomols., and simulations.
- 224NANO-D. INRIA, SAMSON Software, Version ∼0.5.0; http://www.samson-connect.net/, 2016 (Accessed: 09 February 2018).There is no corresponding record for this reference.
- 225Bosson, M.; Richard, C.; Plet, A.; Grudinin, S.; Redon, S. Interactive Quantum Chemistry: A Divide-and-Conquer ASED-MO Method. J. Comput. Chem. 2012, 33, 779– 790, DOI: 10.1002/jcc.22905225https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xkt1Gksw%253D%253D&md5=892979e833f4d542fe8634c28157fd7eInteractive quantum chemistry: A divide-and-conquer ASED-MO methodBosson, Maeel; Richard, Caroline; Plet, Antoine; Grudinin, Sergei; Redon, StephaneJournal of Computational Chemistry (2012), 33 (7), 779-790CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)We present interactive quantum chem. simulation at the atom superposition and electron delocalization MO (ASED-MO) level of theory. Our method is based on the divide-and-conquer (D and C) approach, which we show is accurate and efficient for this non-self-consistent semiempirical theory. The method has a linear complexity in the no. of atoms, scales well with the no. of cores, and has a small prefactor. The time cost is completely controllable, as all steps are performed with direct algorithms, i.e., no iterative schemes are used. We discuss the errors induced by the D and C approach, first empirically on a few examples, and then via a theor. study of two toy models that can be anal. solved for any no. of atoms. Thanks to the precision and speed of the D and C approach, we are able to demonstrate interactive quantum chem. simulations for systems up to a few hundred atoms on a current multicore desktop computer. When drawing and editing mol. systems, interactive simulations provide immediate, intuitive feedback on chem. structures. As the no. of cores on personal computers increases, and larger and larger systems can be dealt with, we believe such interactive simulations-even at lower levels of theory-should thus prove most useful to effectively understand, design and prototype mols., devices and materials. © 2012 Wiley Periodicals, Inc.
- 226Rossi, R.; Isorce, M.; Morin, S.; Flocard, J.; Arumugam, K.; Crouzy, S.; Vivaudou, M.; Redon, S. Adaptive Torsion-Angle Quasi-Statics: A General Simulation Method with Applications to Protein Structure Analysis and Design. Bioinformatics 2007, 23, i408– i417, DOI: 10.1093/bioinformatics/btm191There is no corresponding record for this reference.
- 227Bosson, M.; Grudinin, S.; Bouju, X.; Redon, S. Interactive Physically-Based Structural Modeling of Hydrocarbon Systems. J. Comput. Phys. 2012, 231, 2581– 2598, DOI: 10.1016/j.jcp.2011.12.006227https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1Ogsbw%253D&md5=597f128c081cf549f0ef8667d746861cInteractive physically-based structural modeling of hydrocarbon systemsBosson, Mael; Grudinin, Sergei; Bouju, Xavier; Redon, StephaneJournal of Computational Physics (2012), 231 (6), 2581-2598CODEN: JCTPAH; ISSN:0021-9991. (Elsevier Inc.)Hydrocarbon systems have been intensively studied via numerical methods, including electronic structure computations, mol. dynamics and Monte Carlo simulations. Typically, these methods require an initial structural model (at. positions and types, topol., etc.) that may be produced using scripts and/or modeling tools. For many systems, however, these building methods may be ineffective, as the user may have to specify the positions of numerous atoms while maintaining structural plausibility. In this paper, we present an interactive phys.-based modeling tool to construct structural models of hydrocarbon systems. As the user edits the geometry of the system, at. positions are also influenced by the Brenner potential, a well-known bond-order reactive potential. In order to be able to interactively edit systems contg. numerous atoms, we introduce a new adaptive simulation algorithm, as well as a novel algorithm to incrementally update the forces and the total potential energy based on the list of updated relative at. positions. The computational cost of the adaptive simulation algorithm depends on user-defined error thresholds, and our potential update algorithm depends linearly with the no. of updated bonds. This allows us to enable efficient phys.-based editing, since the computational cost is decoupled from the no. of atoms in the system. We show that our approach may be used to effectively build realistic models of hydrocarbon structures that would be difficult or impossible to produce using other tools.
- 229Jaillet, L.; Artemova, S.; Redon, S. IM-UFF: Extending the Universal Force Field for Interactive Molecular Modeling. J. Mol. Graphics Modell. 2017, 77, 350– 362, DOI: 10.1016/j.jmgm.2017.08.023229https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFGht7zL&md5=d8a6e882b109aa01ac2ce81758ec234bIM-UFF: Extending the universal force field for interactive molecular modelingJaillet, Leonard; Artemova, Svetlana; Redon, StephaneJournal of Molecular Graphics & Modelling (2017), 77 (), 350-362CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)The universal force field (UFF) is a broadly applicable classical force field that contains parameters for almost every atom type of the periodic table. This force field is non-reactive, i.e. the topol. of the system under study is considered as fixed and no creation or breaking of covalent bonds is possible. This paper introduces interactive modeling-UFF (IM-UFF), an extension of UFF that combines the possibility to significantly modify mol. structures (as with reactive force fields) with a broad diversity of supported systems thanks to the universality of UFF. Such an extension lets the user easily build and edit mol. systems interactively while being guided by physics based inter-at. forces. This approach introduces weighted atom types and weighted bonds, used to update topologies and atom parameterizations at every time step of a simulation. IM-UFF has been evaluated on a large set of benchmarks and is proposed as a self-contained implementation integrated in a new module for the SAMSON software platform for computational nanoscience available at http://www.samson-connect.net.
- 230Disz, T.; Papka, M.; Stevens, R.; Pellegrino, M.; Taylor, V. Virtual Reality Visualization of Parallel Molecular Dynamics Simulation. Proceedings of High-Performance Computing 1995, 483– 487There is no corresponding record for this reference.
- 232Salvadori, A.; Del Frate, G.; Pagliai, M.; Mancini, G.; Barone, V. Immersive Virtual Reality in Computational Chemistry: Applications to the Analysis of QM and MM Data. Int. J. Quantum Chem. 2016, 116, 1731– 1746, DOI: 10.1002/qua.25207232https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFCrurnF&md5=bbfba250da95eba7fbd0583621fcb11dImmersive virtual reality in computational chemistry: Applications to the analysis of QM and MM dataSalvadori, Andrea; Del Frate, Gianluca; Pagliai, Marco; Mancini, Giordano; Barone, VincenzoInternational Journal of Quantum Chemistry (2016), 116 (22), 1731-1746CODEN: IJQCB2; ISSN:0020-7608. (John Wiley & Sons, Inc.)The role of Virtual Reality (VR) tools in mol. sciences is analyzed in this contribution through the presentation of the Caffeine software to the quantum chem. community. Caffeine, developed at Scuola Normale Superiore, is specifically tailored for mol. representation and data visualization with VR systems, such as VR theaters and helmets. Usefulness and advantages that can be gained by exploiting VR are here reported, considering few examples specifically selected to illustrate different level of theory and mol. representation.
- 235Sauer, C.; Hastings, W.; Okamura, A. M. Virtual Environment for Exploring Atomic Bonding. Proceedings of EuroHaptics 2004; International Design Foundation, 2004; pp 232– 239.There is no corresponding record for this reference.
- 236Norrby, M.; Grebner, C.; Eriksson, J.; Boström, J. Molecular Rift: Virtual Reality for Drug Designers. J. Chem. Inf. Model. 2015, 55, 2475– 2484, DOI: 10.1021/acs.jcim.5b00544236https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslGjurrL&md5=9a206f1ec098ca25df4a6b81f217891fMolecular Rift: Virtual Reality for Drug DesignersNorrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Bostroem, JonasJournal of Chemical Information and Modeling (2015), 55 (11), 2475-2484CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate phys. presence in the real world-a virtual reality. This is relevant to drug discovery since mol. models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Mol. Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for std. input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Mol. Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chem. and education. Mol. Rift is open source and can be downloaded from GitHub.
- 240Stocks, M. B.; Hayward, S.; Laycock, S. D. Interacting with the Biomolecular Solvent Accessible Surface via a Haptic Feedback Device. BMC Struct. Biol. 2009, 9, 69, DOI: 10.1186/1472-6807-9-69240https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjkvVegtw%253D%253D&md5=863ad1d411a653bccac4b93267584afbInteracting with the biomolecular solvent accessible surface via a haptic feedback deviceStocks Matthew B; Hayward Steven; Laycock Stephen DBMC structural biology (2009), 9 (), 69 ISSN:.BACKGROUND: From the 1950s computer based renderings of molecules have been produced to aid researchers in their understanding of biomolecular structure and function. A major consideration for any molecular graphics software is the ability to visualise the three dimensional structure of the molecule. Traditionally, this was accomplished via stereoscopic pairs of images and later realised with three dimensional display technologies. Using a haptic feedback device in combination with molecular graphics has the potential to enhance three dimensional visualisation. Although haptic feedback devices have been used to feel the interaction forces during molecular docking they have not been used explicitly as an aid to visualisation. RESULTS: A haptic rendering application for biomolecular visualisation has been developed that allows the user to gain three-dimensional awareness of the shape of a biomolecule. By using a water molecule as the probe, modelled as an oxygen atom having hard-sphere interactions with the biomolecule, the process of exploration has the further benefit of being able to determine regions on the molecular surface that are accessible to the solvent. This gives insight into how awkward it is for a water molecule to gain access to or escape from channels and cavities, indicating possible entropic bottlenecks. In the case of liver alcohol dehydrogenase bound to the inhibitor SAD, it was found that there is a channel just wide enough for a single water molecule to pass through. Placing the probe coincident with crystallographic water molecules suggests that they are sometimes located within small pockets that provide a sterically stable environment irrespective of hydrogen bonding considerations. CONCLUSION: By using the software, named HaptiMol ISAS (available from http://www.haptimol.co.uk), one can explore the accessible surface of biomolecules using a three-dimensional input device to gain insights into the shape and water accessibility of the biomolecular surface that cannot be so easily attained using conventional molecular graphics software.
- 243Sourina, O.; Torres, J.; Wang, J. In Transactions on Edutainment II; Pan, Z., Cheok, A. D., Müller, W., Rhalibi, A. E., Eds.; Springer: Berlin, Heidelberg, 2009; Chapter Visual Haptic-Based Biomolecular Docking and Its Applications in E-Learning, pp 105– 118.There is no corresponding record for this reference.
- 245Chastine, J. W.; Zhu, Y.; Brooks, J. C.; Owen, G. S.; Harrison, R. W.; Weber, I. T. A Collaborative Multi-View Virtual Environment for Molecular Visualization and Modeling. Coordinated and Multiple Views in Exploratory Visualization; IEEE, 2005; pp 77– 84.There is no corresponding record for this reference.
- 248Davies, E.; Tew, P.; Glowacki, D.; Smith, J.; Mitchell, T. Evolutionary and Biologically Inspired Music, Sound, Art and Design. Proceedings of the 5th International Conference, EvoMUSART 2016, Porto, Portugal, March 30 – April 1, 2016; Johnson, C., Ciesielski, V., Correia, J. a., Machado, P., Eds.; Springer International Publishing, 2016; pp 17– 30.There is no corresponding record for this reference.
- 250Marti, K. H.; Reiher, M. Haptic Quantum Chemistry. J. Comput. Chem. 2009, 30, 2010– 2020, DOI: 10.1002/jcc.21201250https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXptleqsLw%253D&md5=a0b7305f8d60a1b2a5c8bf5938d6f2a5Haptic quantum chemistryMarti, Konrad H.; Reiher, MarkusJournal of Computational Chemistry (2009), 30 (13), 2010-2020CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)We present an implementation designed to phys. experience quantum mech. forces between reactants in chem. reactions. This allows one to screen the profile of potential energy surfaces for the study of reaction mechanisms. For this, we have developed a interface between the user and a virtual lab. by means of a force-feedback haptic device. Potential energy surfaces of chem. reactions can be explored efficiently by rendering in the haptic device the gradients calcd. with first-principles methods. The underlying potential energy surface is accurately fitted on the fly by the interpolating moving least-squares (IMLS) scheme to a grid of quantum chem. electronic energies (and geometric gradients). In addn., we introduce a new IMLS-based method to locate min.-energy paths between two points on a potential energy surface. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009.
- 251Haag, M. P.; Marti, K. H.; Reiher, M. Generation of Potential Energy Surfaces in High Dimensions and Their Haptic Exploration. ChemPhysChem 2011, 12, 3204– 3213, DOI: 10.1002/cphc.201100539251https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFKrtLjL&md5=df3aa356658e41578110e6b4dd5228aaGeneration of Potential Energy Surfaces in High Dimensions and Their Haptic ExplorationHaag, Moritz P.; Marti, Konrad H.; Reiher, MarkusChemPhysChem (2011), 12 (17), 3204-3213CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)A method is proposed for the automated generation of potential energy surfaces in high dimensions. It combines the existing algorithm for the definition of new energy data points, based on the interpolating moving least-squares algorithm with a simulated annealing procedure. This method is then studied in a haptic quantum chem. environment that requires a fast evaluation of gradients on a potential energy surface with automatic improvement of its accuracy. As an example we investigate the nitrogen binding pathway in the Schrock dinitrogen fixation complex with this set-up.
- 252Haag, M. P.; Reiher, M. Real-Time Quantum Chemistry. Int. J. Quantum Chem. 2013, 113, 8– 20, DOI: 10.1002/qua.24336252https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVykt7fP&md5=ec7746303ee168218745cb0b4539fdb9Real-time quantum chemistryHaag, Moritz P.; Reiher, MarkusInternational Journal of Quantum Chemistry (2013), 113 (1), 8-20CODEN: IJQCB2; ISSN:0020-7608. (John Wiley & Sons, Inc.)Significant progress in the development of efficient and fast algorithms for quantum chem. calcns. has been made in the past two decades. The main focus has always been the desire to be able to treat ever larger mols. or mol. assemblies-esp. linear and sublinear scaling techniques are devoted to the accomplishment of this goal. However, as many chem. reactions are rather local, they usually involve only a limited no. of atoms so that models of about 200 (or even less) atoms embedded in a suitable environment are sufficient to study their mechanisms. Thus, the system size does not need to be enlarged, but remains const. for reactions of this type that can be described by less than 200 atoms. The question then arises how fast one can obtain the quantum chem. results. This question is not directly answered by linear-scaling techniques. In fact, ideas such as haptic quantum chem. (HQC) or interactive quantum chem. require an immediate provision of quantum chem. information which demands the calcn. of data in "real time." In this perspective, we aim at a definition of real-time quantum chem., explore its realm and eventually discuss applications in the field of HQC. For the latter, we elaborate whether a direct approach is possible by virtue of real-time quantum chem. © 2012 Wiley Periodicals, Inc.
- 253Haag, M. P.; Reiher, M. Studying Chemical Reactivity in a Virtual Environment. Faraday Discuss. 2014, 169, 89– 118, DOI: 10.1039/C4FD00021H253https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7nF&md5=8b0b85c38bb608e1d9b8b6fa79ef8760Studying chemical reactivity in a virtual environmentHaag, Moritz P.; Reiher, MarkusFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 89-118CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Chem. reactivity of a set of reactants is detd. by its potential (electronic) energy (hyper)surface. The high dimensionality of this surface renders it difficult to efficiently explore reactivity in a large reactive system. Exhaustive sampling techniques and search algorithms are not straightforward to employ as it is not clear which explored path will eventually produce the min. energy path of a reaction passing through a transition structure. Here, the chemist's intuition would be of invaluable help, but it cannot be easily exploited because (1) no intuitive and direct tool for the scientist to manipulate mol. structures is currently available and because (2) quantum chem. calcns. are inherently expensive in terms of computational effort. In this work, we elaborate on how the chemist can be reintroduced into the exploratory process within a virtual environment that provides immediate feedback and intuitive tools to manipulate a reactive system. We work out in detail how this immersion should take place. We provide an anal. of modern semi-empirical methods which already today are candidates for the interactive study of chem. reactivity. Implications of manual structure manipulations for their phys. meaning and chem. relevance are carefully analyzed in order to provide sound theor. foundations for the interpretation of the interactive reactivity exploration.
- 254Haag, M. P.; Vaucher, A. C.; Bosson, M.; Redon, S.; Reiher, M. Interactive Chemical Reactivity Exploration. ChemPhysChem 2014, 15, 3301– 3319, DOI: 10.1002/cphc.201402342254https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFSgsrnM&md5=5c26a58bb25aa70f7a71ebf0c93ea3ccInteractive Chemical Reactivity ExplorationHaag, Moritz P.; Vaucher, Alain C.; Bosson, Mael; Redon, Stephane; Reiher, MarkusChemPhysChem (2014), 15 (15), 3301-3319CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)Elucidating chem. reactivity in complex mol. assemblies of a few hundred atoms is, despite the remarkable progress in quantum chem., still a major challenge. Black-box search methods to find intermediates and transition-state structures might fail in such situations because of the high-dimensionality of the potential energy surface. Here, we propose the concept of interactive chem. reactivity exploration to effectively introduce the chemist's intuition into the search process. We employ a haptic pointer device with force feedback to allow the operator the direct manipulation of structures in three dimensions along with simultaneous perception of the quantum mech. response upon structure modification as forces. We elaborate on the details of how such an interactive exploration should proceed and which tech. difficulties need to be overcome. All reactivity-exploration concepts developed for this purpose have been implemented in the SAMSON programming environment.
- 256Atsumi, T.; Nakai, H. Molecular Orbital Propagation to Accelerate Self-Consistent-Field Convergence in an Ab Initio Molecular Dynamics Simulation. J. Chem. Phys. 2008, 128, 094101, DOI: 10.1063/1.2839857256https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXjtl2qt74%253D&md5=1b02d7ccbc0390afd6bc6421fe3d2f36Molecular orbital propagation to accelerate self-consistent-field convergence in an ab initio molecular dynamics simulationAtsumi, Teruo; Nakai, HiromiJournal of Chemical Physics (2008), 128 (9), 094101/1-094101/9CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Based on the idea of MO propagation, we propose a novel effective method for predicting initial guesses for the self-consistent-field calcns. in direct ab initio mol. dynamics (AIMD) simulations. This method, called LIMO, adopts the Lagrange interpolation (LI) polynomial technique and predicts initial MO coeffs. at the next AIMD step by using several previous results. Taking into account the crossing and/or mixing of MOs leads to orbital invariant formulas for the LIMO method. We also propose a simple method for detg. the optimal degree of the LI polynomial, which corresponds to the no. of previous steps. Numerical tests confirm that this proposed method is both effective and feasible. (c) 2008 American Institute of Physics.
- 257Atsumi, T.; Nakai, H. Acceleration of Self-Consistent-Field Convergence in Ab Initio Molecular Dynamics and Monte Carlo Simulations and Geometry Optimization. Chem. Phys. Lett. 2010, 490, 102– 108, DOI: 10.1016/j.cplett.2010.03.012257https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkt1ygt74%253D&md5=378feecb4e22a46ab096a8c43c0e5a9eAcceleration of self-consistent-field convergence in ab initio molecular dynamics and Monte Carlo simulations and geometry optimizationAtsumi, Teruo; Nakai, HiromiChemical Physics Letters (2010), 490 (1-3), 102-108CODEN: CHPLBC; ISSN:0009-2614. (Elsevier B.V.)We propose a novel acceleration method for self-consistent-field calcns. in direct ab initio mol. dynamics/Monte Carlo (AIMD/AIMC) simulations and geometry optimization. This acceleration method, so-called LSMO, predicts an initial guess of MOs (MOs) for the next simulation step by using the geometric information with the least-squares technique. Numerical tests confirm that the LSMO method is both effective and feasible in the AIMD/AIMC simulations and geometry optimization.
- 258Vaucher, A. C.; Haag, M. P.; Reiher, M. Real-Time Feedback from Iterative Electronic Structure Calculations. J. Comput. Chem. 2016, 37, 805– 812, DOI: 10.1002/jcc.24268258https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVCltLrK&md5=847dceab1dfd98f653c508db8961b9adReal-time feedback from iterative electronic structure calculationsVaucher, Alain C.; Haag, Moritz P.; Reiher, MarkusJournal of Computational Chemistry (2016), 37 (9), 805-812CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Real-time feedback from iterative electronic structure calcns. requires to mediate between the inherently unpredictable execution times of the iterative algorithm used and the necessity to provide data in fixed and short time intervals for real-time rendering. We introduce the concept of a mediator as a component able to deal with infrequent and unpredictable ref. data to generate reliable feedback. In the context of real-time quantum chem., the mediator takes the form of a surrogate potential that has the same local shape as the first-principles potential and can be evaluated efficiently to deliver at. forces as real-time feedback. The surrogate potential is updated continuously by electronic structure calcns. and guarantees to provide a reliable response to the operator for any mol. structure. To demonstrate the application of iterative electronic structure methods in real-time reactivity exploration, we implement self-consistent semiempirical methods as the data source and apply the surrogate-potential mediator to deliver reliable real-time feedback. © 2015 Wiley Periodicals, Inc.
- 259Vaucher, A. C.; Reiher, M. Steering Orbital Optimization out of Local Minima and Saddle Points Toward Lower Energy. J. Chem. Theory Comput. 2017, 13, 1219– 1228, DOI: 10.1021/acs.jctc.7b00011259https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivVKqs78%253D&md5=94b5a248bcc23b8c0d0e71e82c8be2f1Steering Orbital Optimization out of Local Minima and Saddle Points Toward Lower EnergyVaucher, Alain C.; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (3), 1219-1228CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The general procedure underlying Hartree-Fock and Kohn-Sham d. functional theory calcns. consists in optimizing orbitals for a self-consistent soln. of the Roothaan-Hall equations in an iterative process. It is often ignored that multiple self-consistent solns. can exist, several of which may correspond to min. of the energy functional. In addn. to the difficulty sometimes encountered to converge the calcn. to a self-consistent soln., one must ensure that the correct self-consistent soln. was found, typically the one with the lowest electronic energy. Convergence to an unwanted soln. is in general not trivial to detect and will deliver incorrect energy and mol. properties and accordingly a misleading description of chem. reactivity. Wrong conclusions based on incorrect SCF convergence are particularly cumbersome in automated calcns. met in high-throughput virtual screening, structure optimizations, ab initio mol. dynamics, and in real-time explorations of chem. reactivity, where the vast amt. of data can hardly be manually inspected. Here, we introduce a fast and automated approach to detect and cure incorrect orbital convergence, which is esp. suited for electronic structure calcns. on sequences of mol. structures. Our approach consists of a randomized perturbation of the converged electron d. (matrix) intended to push orbital convergence to solns. that correspond to another stationary point (of potentially lower electronic energy) in the variational parameter space of an electronic wave function approxn.
- 260Vaucher, A. C.; Reiher, M. Molecular Propensity as a Driver for Explorative Reactivity Studies. J. Chem. Inf. Model. 2016, 56, 1470– 1478, DOI: 10.1021/acs.jcim.6b00264260https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xht1WntbrN&md5=ba5071e8f71e85291382737cf389899aMolecular Propensity as a Driver for Explorative Reactivity StudiesVaucher, Alain C.; Reiher, MarkusJournal of Chemical Information and Modeling (2016), 56 (8), 1470-1478CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Quantum chem. studies of reactivity involve calcns. on a large no. of mol. structures and the comparison of their energies. Already the setup of these calcns. limits the scope of the results that one will obtain, because several system-specific variables such as the charge and spin need to be set prior to the calcn. For a reliable exploration of reaction mechanisms, a considerable no. of calcns. with varying global parameters must be taken into account, or important facts about the reactivity of the system under consideration can remain undetected. For example, one could miss crossings of potential energy surfaces for different spin states or might not note that a mol. is prone to oxidn. Here, we introduce the concept of mol. propensity to account for the predisposition of a mol. system to react across different electronic states in certain nuclear configurations or with other reactants present in the reaction liquor. Within our real-time quantum chem. framework, we developed an algorithm that automatically detects and flags such a propensity of a system under consideration.
- 261Heuer, M. A.; Vaucher, A. C.; Haag, M. P.; Reiher, M. Integrated Reaction Path Processing from Sampled Structure Sequences. J. Chem. Theory Comput. 2018, 14, 2052– 2062, DOI: 10.1021/acs.jctc.8b00019261https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXktFWgs78%253D&md5=aa7c203a39a0cc9c876174b2c517e4c5Integrated Reaction Path Processing from Sampled Structure SequencesHeuer, Michael A.; Vaucher, Alain C.; Haag, Moritz P.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (4), 2052-2062CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Sampled structure sequences obtained, for instance, from real-time reactivity explorations or first-principles mol. dynamics simulations contain valuable information about chem. reactivity. Eventually, such sequences allow for the construction of reaction networks that are required for the kinetic anal. of chem. systems. For this purpose, however, the sampled information must be processed to obtain stable chem. structures and assocd. transition states. The manual extn. of valuable information from such reaction paths is straightforward but unfeasible for large and complex reaction networks. For real-time quantum chem., this implies automatization of the extn. and relaxation process while maintaining immersion in the virtual chem. environment. Here, we describe an efficient path processing scheme for the on-the-fly construction of an exploration network by approximating the explored paths as continuous basis-spline curves.
- 262Reiher, M.; SCINE – Software for Chemical Interaction Networks. http://scine.ethz.ch (Accessed: 12. September 2018).There is no corresponding record for this reference.
