Weighted ensemble simulations with the Drude polarizable model

Abstract

Enhanced sampling methods have become powerful techniques to investigate complex systems and rare molecular events by facilitating greater access to configurational space. In parallel, the continuous development of polarizable force fields augments such techniques, allowing the investigation of the role of electronic polarization in transitional barriers that might be overlooked in nonpolarizable simulations. Together, improved sampling methods and polarizable force fields should accelerate computational discoveries. Here, we present an implementation of a weighted ensemble strategy for the Drude polarizable force field using the WESTPA software package in conjunction with the OpenMM simulation engine. We demonstrate its use for backbone conformational sampling in a model system (alanine dipeptide) and in studying functional sidechain rotations in an enzyme (Abl1 kinase). We further discuss possible consequences related to the inclusion of explicit electronic polarization in the model. This software implementation and validation should facilitate the use of WESTPA-Drude strategies throughout the simulation community.