Work

Nonadiabatic Force Matching for Alchemical Free-Energy Estimation

Year: 2025

Type: article

Abstract: We propose a method to compute free-energy differences from nonadiabatic alchemical transformations by using flow-based generative models. The method, nonadiabatic force matching, hinges on estimating the dissipation along an alchemical switching process in terms of a nonadiabatic force field that can be learned through stochastic flow matching. The learned field can be used in conjunction with short-time trajectory data to evaluate upper and lower bounds on the alchemical free energy that variationally converge to the exact value if the field is optimal. Applying the method to evaluate the alchemical free energy of atomistic models shows that it can substantially reduce the simulation cost of a free-energy estimate at a negligible loss of accuracy when compared with thermodynamic integration.

Source: Journal of Chemical Theory and Computation

DOI: 10.1021/acs.jctc.5c01478

Authors: Jorge L. Rosa-Raíces, David T. Limmer

Institutions: Lawrence Berkeley National Laboratory, Kavli Energy NanoScience Institute

Language: English

Topic: Advanced Physical and Chemical Molecular Interactions

Subfield: Physical and Theoretical Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Division of Materials Research, Basic Energy Sciences

Awards: G214348771, G5579095734