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

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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.