Thermodynamic Interpolation: A Generative Approach to Molecular Thermodynamics and Kinetics
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| Title: | Thermodynamic Interpolation: A Generative Approach to Molecular Thermodynamics and Kinetics |
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| Authors: | Moqvist, Selma, 2000, Chen, Weilong, Schreiner, Jacob Mathias, 1991, Nueske, Feliks, Olsson, Simon, 1985 |
| Source: | From atom to organism: Bridging the scales in the design of ion channel drugs Journal of Chemical Theory and Computation Thermodynamic Interpolation: Data, splits and model weights. 21(5):2535-2545 |
| Subject Terms: | Mathematical methods, Computer simulations, Kinetics, Thermodynamics, Free energy |
| Description: | 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). |
| File Description: | electronic |
| Access URL: | https://research.chalmers.se/publication/545517 https://research.chalmers.se/publication/545517/file/545517_Fulltext.pdf |
| Database: | SwePub |
Nájsť tento článok vo Web of Science | 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 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). |
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| ISSN: | 15499626 15499618 |
| DOI: | 10.1021/acs.jctc.4c01557 |