Bayesian umbrella quadrature accelerates free-energy calculations across diverse molecular systems and processes

TL;DR

Bayesian Umbrella Quadrature (BUQ) enhances free-energy calculations in molecular dynamics by automating biasing protocol selection, leading to improved accuracy and efficiency across various molecular systems.

Contribution

The paper introduces BUQ, a novel Bayesian method that automates biasing in umbrella sampling, reducing manual tuning and improving robustness in free-energy calculations.

Findings

Achieved high accuracy in peptide conformational change

Demonstrated speedups in phase transition simulations

Validated across chemical reactions

Abstract

Biased sampling in molecular dynamics simulations overcomes timescale limitations and delivers free-energy landscapes, essential to understand complex atomistic phenomena. However, when applied across diverse systems and processes, biasing protocols often require time- and resource-consuming fine-tuning. In search for robustness, we boost a prominent biasing method, Umbrella Sampling. To estimate the value of an integral, i.e., the free energy, our Bayesian Umbrella Quadrature (BUQ) method iteratively selects gradient samples, i.e., bias locations, that most reduce the posterior integral variance based on a noise-tolerant Gaussian process model, which also effectively interpolates between samples. We validate the method for a conformational change in a small peptide, a water-to-ice phase transition, and a substitution chemical reaction; obtaining excellent accuracies and speedups. To ease adoption of this more automated and universal free-energy method, we interface BUQ with wide-spread simulation packages and share hyperparametrization guidelines.