Accelerating Molecular Dynamics through Informed Resetting

TL;DR

This paper introduces an informed stochastic resetting method to accelerate molecular dynamics simulations, significantly improving sampling efficiency and enabling accurate kinetic measurements in complex molecular processes.

Contribution

The authors develop a novel informed resetting protocol that outperforms standard resetting by utilizing reaction progress information, extending stochastic resetting's applicability in molecular simulations.

Findings

Achieves 2-3 orders of magnitude speedup in Metadynamics simulations.

Provides accurate estimates of mean first-passage and transit times.

Demonstrates effectiveness on protein folding and nucleation models.

Abstract

We present a procedure for enhanced sampling of molecular dynamics simulations through informed stochastic resetting. Many phenomena, such as protein folding and crystal nucleation, occur over time scales that are inaccessible in standard simulations. We recently showed that stochastic resetting can accelerate molecular simulations that exhibit broad transition time distributions. However, standard stochastic resetting does not exploit any information about the reaction progress. For a model system and chignolin in explicit water, we demonstrate that an informed resetting protocol leads to greater accelerations than standard stochastic resetting in molecular dynamics and Metadynamics simulations. This is achieved by resetting only when a certain condition is met, e.g., when the distance from the target along the reaction coordinate is larger than some threshold. We use these accelerated simulations to infer important kinetic observables such as the unbiased mean first-passage time and direct transit time. For the latter, Metadynamics with informed resetting leads to speedups of 2-3 orders of magnitude over unbiased simulations with relative errors of only ~35-70%. Our work significantly extends the applicability of stochastic resetting for enhanced sampling of molecular simulations.