Solvation Free Energies from Neural Thermodynamic Integration

Bálint Máté; François Fleuret; Tristan Bereau

doi:10.1063/5.0251736

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arXiv · 2410.15815

Solvation Free Energies from Neural Thermodynamic Integration

Bálint Máté·François Fleuret·Tristan Bereau

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Abstract

We present a method for computing free-energy differences using thermodynamic integration with a neural network potential that interpolates between two target Hamiltonians. The interpolation is defined at the sample distribution level, and the neural network potential is optimized to match the corresponding equilibrium potential at every intermediate time-step. Once the interpolating potentials and samples are well-aligned, the free-energy difference can be estimated using (neural) thermodynamic integration. To target molecular systems, we simultaneously couple Lennard-Jones and electrostatic interactions and model the rigid-body rotation of molecules. We report accurate results for several benchmark systems: a Lennard-Jones particle in a Lennard-Jones fluid, as well as the insertion of both water and methane solutes in a water solvent at atomistic resolution using a simple three-body neural-network potential.

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Bálint Máté, François Fleuret, Tristan Bereau. 2024-10-21. Solvation Free Energies from Neural Thermodynamic Integration. https://doi.org/10.1063/5.0251736

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