Calculation of the potential of mean force from nonequilibrium measurements via maximum likelihood estimators

TL;DR

This paper introduces a maximum likelihood-based method to estimate the potential of mean force from nonequilibrium measurements, providing accurate free energy calculations for biomolecular processes.

Contribution

It develops a novel maximum likelihood approach that unifies various free energy estimators for systems driven far from equilibrium.

Findings

Accurately estimates potential of mean force from nonequilibrium data

Achieves results comparable to thermodynamic integration

Applicable to biomolecular unfolding processes

Abstract

We present an approach to the estimate of the potential of mean force along a generic reaction coordinate based on maximum likelihood methods and path-ensemble averages in systems driven far from equilibrium. Following similar arguments, various free energy estimators can be recovered, all providing comparable computational accuracy. The method, applied to the unfolding process of the alpha-helix form of an alanine deca-peptide, gives results in good agreement with thermodynamic integration.