Weighted Ensemble Simulations With the Drude Polarizable Model

TL;DR

This paper introduces a new method combining polarizable models with enhanced sampling to study molecular systems more accurately.

Contribution

The novel contribution is implementing a weighted ensemble strategy with the Drude polarizable model in the WESTPA and OpenMM platforms.

Findings

The method was successfully applied to alanine dipeptide and Abl1 kinase systems.

Electronic polarization significantly impacts conformational sampling and sidechain flipping mechanisms.

The implementation facilitates broader use of polarizable models in enhanced sampling simulations.

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.

We demonstrate the combination of the Drude polarizable force field with the WESTPA enhanced‐sampling method in the OpenMM software. Our results demonstrate the facile interaction of these two techniques and how electronic polarization impacts conformational sampling in a model alanine dipeptide system and a kinase sidechain flipping mechanism.

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