Matching of Additive and Polarizable Force Fields for Multiscale Condensed Phase Simulations

Abstract

Inclusion of electronic polarization effects is one of the key aspects in which the accuracy of current biomolecular force fields may be improved. The principal drawback of such approaches is the computational cost, which typically ranges from 3 - 10 times that of the equivalent additive model, and may be greater for more sophisticated treatments of polarization or other many-body effects. Here, we present a multiscale approach which may be used to enhance the sampling in simulations with polarizable models, by using the additive model as a tool to explore configuration space. We use a method based on information theory to determine the charges for an additive model that has optimal overlap with the polarizable one, and we demonstrate the feasibility of enhancing sampling via a hybrid replica exchange scheme for several model systems. An additional advantage is that, in the process, we obtain a systematic method for deriving charges for an additive model that will be the natural complement to its polarizable parent. The additive charges are found by an effective coarse-graining of the polarizable force field, rather than by ad hoc procedures.