Thermodynamic Interpolation: A Generative Approach to Molecular Thermodynamics and Kinetics
Artikel i vetenskaplig tidskrift, 2025

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 nontrivial 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).

Mathematical methods

Computer simulations

Kinetics

Free energy

Thermodynamics

Författare

Selma Moqvist

Chalmers, Data- och informationsteknik, Data Science och AI

Göteborgs universitet

Weilong Chen

Göteborgs universitet

Chalmers, Data- och informationsteknik

Jacob Mathias Schreiner

Chalmers, Data- och informationsteknik, Data Science och AI

Göteborgs universitet

Feliks Nueske

Max-Planck-Gesellschaft

Simon Olsson

Chalmers, Data- och informationsteknik, Data Science och AI

Göteborgs universitet

Journal of Chemical Theory and Computation

1549-9618 (ISSN) 1549-9626 (eISSN)

Vol. 21 5 2535-2545

Ämneskategorier (SSIF 2025)

Den kondenserade materiens fysik

DOI

10.1021/acs.jctc.4c01557

PubMed

39988824

Mer information

Senast uppdaterat

2025-03-26