Thermodynamic Interpolation: A generative approach to molecular thermodynamics and kinetics

2024/11/15 by Selma Moqvist, Weilong Chen, Moqvist, Selma +7 · 7 citations
Physics and Astronomy · #Advanced Thermodynamics and Statistical Mechanics #Chemical Physics (physics.chem-ph) #FOS: Physical sciences

paper · pdf · doi:10.48550/arxiv.2411.10075

openalex publication_date 2024/11/15 · openalex created_date 2024/11/21 · openalex updated_date 2026/07/28

Abstract

Using normalizing flows and reweighting, Boltzmann Generators enable equilibrium sampling from a Boltzmann distribution, defined by an energy function and thermodynamic state. In this work, we introduce Thermodynamic Interpolation (TI), which allows for generating sampling statistics in a temperature-controllable way. We introduce TI flavors that work directly in the ambient configurational space, mapping between different thermodynamic states or through a latent, normally distributed reference state. Our ambient-space approach allows for the specification of arbitrary target temperatures, ensuring generalizability within the temperature range of the training set and demonstrating the potential for extrapolation beyond it. We validate the effectiveness of TI on model systems that exhibit metastability and non-trivial temperature dependencies. Finally, we demonstrate how to combine TI-based sampling to estimate free energy differences through various free energy perturbation methods and provide corresponding approximated kinetic rates estimated through generator extended dynamic mode decomposition (gEDMD).

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