Implementation of Girsanov Reweighting in OpenMM and Deeptime.

Abstract

Classical molecular dynamics (MD) simulations provide invaluable insights into complex molecular systems but face limitations in capturing phenomena occurring on time scales beyond their reach. To bridge this gap, various enhanced sampling techniques have been developed, which are complemented by reweighting techniques to recover the unbiased dynamics. Girsanov reweighting is a reweighting technique that reweights simulation paths, generated by a stochastic MD integrator, without evoking an effective model of the dynamics. Instead, it calculates the relative path probability density at the time resolution of the MD integrator. Efficient implementation of Girsanov reweighting requires that the reweighting factors are calculated on-the-fly during the simulations and thus needs to be implemented within the MD integrator. Here, we present a comprehensive guide for implementing Girsanov reweighting into MD simulations. We demonstrate the implementation in the MD simulation package OpenMM by extending the library openmmtools. Additionally, we implemented a reweighted Markov state model estimator within the time series analysis package Deeptime.