Calculations of the Electric Field in Solutions and Proteins with Polarizable Force Fields

Abstract

A molecule in solution or a ligand bound to a protein experiences a complex range of electrostatic interactions from its environment. One way of describing these interactions in a collective fashion is to consider the total electric field they exert on the molecule of interest. A key advantage of this picture is that it provides a unifying language for comparing the relative importance of diverse specific interactions (e.g., hydrogen bonds) and nonspecific interactions (e.g., dipole-dipole and dipole-induced dipole), and it facilitates direct comparison to experimental observables (like vibrational Stark effects). We develop and demonstrate methods to calculate electric fields using molecular dynamics simulations with the AMOEBA polarizable force field, which enables us to describe the electrostatic characteristics of non-polar, polar, and hydrogen bonding environments in a consistent fashion. This consistency is not achievable with the more widely used continuum models or pair-wise additive force fields. The connection to experiment further enables us to test predictions from simulation and to benchmark the force fields employed. By offering a high-level description of electrostatics, polarizable force fields present a physically realistic picture of the organized environments of proteins and how functional properties emerge from them.