Embedding Quantum Statistical Excitations in a Classical Force Field.

Abstract

Quantum-mechanically driven charge polarization and charge transfer are ubiquitous in biomolecular systems, controlling reaction rates, allosteric interactions, ligand-protein binding, membrane transport, and dynamically driven structural transformations. Molecular dynamics (MD) simulations of these processes require quantum mechanical (QM) information in order to accurately describe their reactive dynamics. However, current techniques-empirical force fields, subsystem approaches, ab initio MD, and machine learning-vary in their ability to achieve a consistent chemical description across multiple atom types, and at scale. Here we present a physics-based, atomistic force field, the ensemble DFT charge-transfer embedded-atom method, in which QM forces are described at a uniform level of theory across all atoms, avoiding the need for explicit solution of the Schrödinger equation or large, precomputed training data sets. Coupling between the electronic and atomistic length scales is effected through an ensemble density functional theory formulation of the embedded-atom method originally developed for elemental materials. Charge transfer is expressed in terms of ensembles of ionic state basis densities of individual atoms, and charge polarization, in terms of atomic excited-state basis densities. This provides a highly compact yet general representation of the force field, encompassing both local and system-wide effects. Charge rearrangement is realized through the evolution of ensemble weights, adjusted at each dynamical time step via chemical potential equalization.