Machine-guided path sampling to discover mechanisms of molecular self-organization
- Author(s)
- Hendrik Jung, Roberto Covino, A. Arjun, Christian Leitold, Christoph Dellago, Peter G. Bolhuis, Gerhard Hummer
- Abstract
Molecular self-organization driven by concerted many-body interactions produces the ordered structures that define both inanimate and living matter. Here we present an autonomous path sampling algorithm that integrates deep learning and transition path theory to discover the mechanism of molecular self-organization phenomena. The algorithm uses the outcome of newly initiated trajectories to construct, validate and—if needed—update quantitative mechanistic models. Closing the learning cycle, the models guide the sampling to enhance the sampling of rare assembly events. Symbolic regression condenses the learned mechanism into a human-interpretable form in terms of relevant physical observables. Applied to ion association in solution, gas-hydrate crystal formation, polymer folding and membrane-protein assembly, we capture the many-body solvent motions governing the assembly process, identify the variables of classical nucleation theory, uncover the folding mechanism at different levels of resolution and reveal competing assembly pathways. The mechanistic descriptions are transferable across thermodynamic states and chemical space.
- Organisation(s)
- Computational and Soft Matter Physics
- External organisation(s)
- Max Planck Institute of Biophysics, Frankfurt Institute for Advanced Studies (FIAS), University of Amsterdam (UvA), Johann Wolfgang Goethe-Universität Frankfurt am Main
- Journal
- Nature Computational Science
- Volume
- 3
- Pages
- 334–345
- No. of pages
- 12
- ISSN
- 2662-8457
- DOI
- https://doi.org/10.1038/s43588-023-00428-z
- Publication date
- 04-2023
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 103006 Chemical physics, 103043 Computational physics, 103029 Statistical physics
- ASJC Scopus subject areas
- Computer Science (miscellaneous), Computer Science Applications, Computer Networks and Communications
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/c22963ee-0f55-41ef-a8d2-a34ac9d57ca5