Variationally Optimized Free Energy Flooding for Rate Calculation

TL;DR

This paper introduces a variationally optimized free energy flooding method to efficiently compute kinetic properties of rare events in molecular dynamics, significantly improving over previous techniques.

Contribution

It develops a novel bias potential construction using a variational approach to accelerate rare event simulations while maintaining accurate transition states.

Findings

Achieves an order of magnitude efficiency improvement over previous methods

Provides several orders of magnitude speedup compared to unbiased simulations

Demonstrates potential for application to complex systems with many collective variables

Abstract

We propose a new method to obtain kinetic properties of infrequent events from molecular dynamics simulation. The procedure employs a recently introduced variational approach [Valsson and Parrinello, Phys. Rev. Lett. 113, 090601 (2014)] to construct a bias potential as a function of several collective variables that is designed to flood only the associated free energy surface up to a predefined level. The resulting bias potential effectively accelerates transitions between metastable free energy minima while ensuring bias-free transition states, thus allowing accurate kinetic rates to be obtained. We test the method on a few illustrative systems for which we obtain an order of magnitude improvement in efficiency relative to previous approaches, and several orders of magnitude relative to unbiased molecular dynamics. We expect an even larger improvement in more complex systems. This and the ability of the variational approach to deal efficiently with a large number of collective variables will greatly enhance the scope of these calculations. This work is a vindication of the potential that the variational principle has if applied in innovative ways