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Neural Thermodynamic Integration: Free Energies from Diffusion Models (arxiv.org)
2 points by jasondavies on Jun 17, 2024 | hide | past | pdf | discuss on HN

In plain words: A neural network learns an energy path between the interacting and non-interacting versions of a system, so one simulation can generate every intermediate state needed for free-energy differences. On simple particle fluids it matched the true free-energy change without separate simulations at each step.

Abstract · Neural Thermodynamic Integration: Free Energies from Energy-based Diffusion Models

Thermodynamic integration (TI) offers a rigorous method for estimating free-energy differences by integrating over a sequence of interpolating conformational ensembles. However, TI calculations are computationally expensive and typically limited to coupling a small number of degrees of freedom due to the need to sample numerous intermediate ensembles with sufficient conformational-space overlap. In this work, we propose to perform TI along an alchemical pathway represented by a trainable neural network, which we term Neural TI. Critically, we parametrize a time-dependent Hamiltonian interpolating between the interacting and non-interacting systems, and optimize its gradient using a score matching objective. The ability of the resulting energy-based diffusion model to sample all intermediate ensembles allows us to perform TI from a single reference calculation. We apply our method to Lennard-Jones fluids, where we report accurate calculations of the excess chemical potential, demonstrating that Neural TI reproduces the underlying changes in free energy without the need for simulations at interpolating Hamiltonians.

Bálint Máté, François Fleuret, Tristan Bereau
arXiv:2406.02313 · cond-mat.stat-mech, cs.LG · submitted Jun 4, 2024 · updated Dec 3, 2024
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