  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
Schr\"{o}dinger equation or large, precomputed training datasets. 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 states 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
timestep via chemical potential equalization.
