Reactive and Non-Reactive Force Field Design Guided by Advances in Energy Decomposition Analysis

加州大学伯克利分校的Teresa Head-Gordon和Martin Head-Gordon获得了化学部化学理论、模型和计算方法项目的支持，以开发先进的力场。在化学研究中，基于计算机的分子模拟是化学反应实验探针不可或缺的补充。模拟用于了解溶剂(通常是分散原料和产品的液体)在化学反应中所起的作用。这样的模拟使用力场来传播分子的运动。力场是一种经验函数，它准确而廉价地描述了系统的势能如何随原子和分子的位置变化。分子模拟通过提高力场的精确度和更好的统计抽样而进步。这项研究的中心目标是以能量分解分析(EDA)的新进展为指导，追求合理的下一代力场设计。EDA对一组分子进行先进的量子力学计算，并将分子的相互作用能量提炼成一系列项，以捕捉排斥力和吸引力的物理驱动力。这些术语为新力场的设计和参数化提供了有价值的数据。这些发展还产生了对其他化学家有用的新计算工具，并在验证和试点应用后作为软件提供给他们。这项研究为研究生提供了非常强大的高级理论、软件开发和化学应用方面的培训。一个新的伯克利分子模拟和软件工程专业硕士项目(MSSE)将于2020年启动，旨在培训计算分子科学、最佳软件工程实践以及推动软件企业发展所需的领导和管理技能方面的研究生。正在为非专业人员开发一个关于计算量子化学的专题课程，使用一本免费提供的电子书，包括在国家科学基金会支持下开发的EDA方法。面向初级转学学生的计算化学(CC-TS)本科研究项目也得到了支持。这项研究的目标是完成蛋白质力场的方法学，推广到其他复杂的凝聚相化学，涉及电子密度的扰动，而不改变成键化学。一种新的EDA能力正在为关键类别的分子内相互作用开发，从而能够物理地洞察构象平衡和扭转势。EDA框架正在扩展，以包括可极化的连续介质溶剂模型，以便能够研究不同介电环境下的分子间相互作用。为了推进凝聚相中反应化学的建模，将利用为非反应模型开发的改进的非键相互作用来产生比当前模型更高的精度，并允许反应和非反应力场的无缝混合。此外，新一代后超临界流体EDA的创建使得能够分析化学键的变化，以更好地表征反应力场中的键级项(或其等价项)。这些模型和方法被部署在选定的应用中，包括评估凝聚相太赫兹光谱观察值，解开溶液和气相中分子扭转平衡物种的驱动力，以及探索静电溶剂化与分子溶剂化在调解物理力中的作用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Teresa Head-Gordon and Martin Head-Gordon of the University of California, Berkeley, are supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry to develop advanced force-fields. In chemical research, computer-based molecular simulations are an indispensible complement to experimental probes of chemical reactions. Simulation is used to understand the role that solvents (usually liquids that disperse the starting materials and products) play in chemical reactions. Such simulations use force fields to propagate the motions of the molecules. Force fields are empirical functions describe how the potential energy of a system varies with the position of the atoms and molecules both accurately and inexpensively. Molecular simulations advance by improving the accuracy of the force field, and via better statistical sampling. The central goal of this research is to pursue rational, next-generation force field design guided by new advances in energy decomposition analysis (EDA). An EDA takes advanced quantum mechanical calculations on groups of molecules, and distills the interaction energy of the molecules into a sum of terms that captures the repulsive and attractive physical driving forces. These terms provide valuable data to inform the design and parameterization of the new force fields. These developments also yield new computational tools that are useful to other chemists, and are made available to them as software, following validation and pilot applications. The research provides very strong training for graduate students in advanced theory, software development, and chemical applications. A new Berkeley Professional Master's program in Molecular Simulation and Software Engineering (MSSE) is launching in 2020, to train post-baccalaureate students in computational molecular science, best software engineering practices, and the leadership and management skills needed to drive software enterprises. A special topics class on computational quantum chemistry for non-specialists using a freely available e-book, including the EDA methods developed under NSF support is being developed. The Computational Chemistry for Transfer Students (CC-TS) undergraduate research program, targeting junior-level transfer students is also supported. The target of this research is the completion of a protein force field with methodology that generalizes to other complex condensed phase chemistry that involves perturbations to the electron density without changing bonded chemistry. A new EDA capability is being developed for key classes of intramolecular interactions enabling physical insight into conformational equilibria and torsional potentials. The EDA framework is being extended to include polarizable continuum solvent models to enable study of intermolecular interactions, under different dielectric environments. To advance modeling of reactive chemistry in the condensed phase, the improved non-bonded interactions developed for the non-reactive models will be utilized to yield higher accuracy than current models and to allow seamless mixing of reactive and non-reactive force fields. Additionally, the creation of a next generation post-SCF EDA enables analysis of changes in chemical bonding to better characterize the bond order terms (or their equivalent) within the reactive force field. These models and methods are deployed for selected applications, including evaluation of condensed phase terahertz spectroscopic observables, unraveling the driving forces of molecular torsion balance species in solution and in gas phase, and probing the role of electrostatic solvation versus molecular solvation in mediating physical forces.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.