Nonadiabatic force matching for alchemical free-energy estimation

Kavli Affiliate: David T. Limmer

| First 5 Authors: Jorge L. Rosa-Raíces, Jorge L. Rosa-Raíces, , ,

| Summary:

We propose a method to compute free energies from nonadiabatic alchemical
transformations using diffusion-denoising generative models. The method,
nonadiabatic force matching, hinges on estimating — rather than minimizing —
the dissipation along an alchemical transition as the functional of a
nonadiabatic potential, which plays the role of a diffusion-denoising protocol.
Applying the algorithm to compute alchemical free energies of simple atomistic
models shows it can significantly cut the simulation cost of a free-energy
estimate at no loss of accuracy compared with thermodynamic integration.

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