Rare Event Kinetics from Adaptive Bias Enhanced Sampling

TL;DR

This paper presents OPES flooding, a new enhanced sampling method for accurately calculating the kinetics of rare events in molecular dynamics, applicable to complex systems with optimized parameters and biasing strategies.

Contribution

It introduces the OPES flooding technique, extending the OPES approach to compute kinetics and providing guidelines for biasing and parameter selection.

Findings

Accurate kinetics require bias-free transition states.

Bias should not exceed the effective barrier height.

Method works with suboptimal order parameters.

Abstract

We introduce a novel enhanced sampling approach named OPES flooding for calculating the kinetics of rare events from atomistic molecular dynamics simulation. This method is derived from the On-the-fly-Probability-Enhanced-Sampling (OPES) approach [Invernizzi and Parrinello, JPC Lett. 2020], which has been recently developed for calculating converged free energy surfaces for complex systems. In this paper, we describe the theoretical details of the OPES flooding technique and demonstrate the application on three systems of increasing complexity: barrier crossing in a two-dimensional double well potential, conformational transition in the alanine dipeptide in gas phase, and the folding and unfolding of the chignolin polypeptide in aqueous environment. From extensive tests, we show that the calculation of accurate kinetics not only requires the transition state to be bias-free, but the amount of bias deposited should also not exceed the effective barrier height measured along the chosen collective variables. In this vein, the possibility of computing rates from biasing suboptimal order parameters has also been explored. Furthermore, we describe the choice of optimum parameter combinations for obtaining accurate results from limited computational effort.