In EDS ansehen

Building multiscale Markov state models by systematic mapping of temporal communities.

Gespeichert in:
Bibliographische Detailangaben
Titel: Building multiscale Markov state models by systematic mapping of temporal communities.
Autoren: Nitskansky, Nir, Clein, Kessem, Raveh, Barak
Quelle: Bioinformatics; Jan2026, Vol. 42 Issue 1, p1-13, 13p
Abstract: Motivation Biomolecules undergo dynamic transitions among metastable states to carry out their biological functions. Markov State Models (MSMs) effectively capture these metastable states and transitions at a defined temporal scale. However, biomolecular dynamics typically span multiple temporal scales, ranging from fast atomic vibrations to slower conformational changes and folding events. Results We introduce multiscale Markov State Models (mMSMs), which capture biomolecular dynamics across multiple temporal resolutions simultaneously via a hierarchy of MSMs, and mMSM-explore, an unsupervised algorithm for generating mMSMs through multiscale adaptive sampling with on-the-fly identification of temporally metastable states. We benchmark our method on a toy system with nested energy minima; on alanine dipeptide, first with and then without assuming prior knowledge of its two reaction coordinates; and finally, on a fast-folding 35-residue miniprotein, where we map folding pathways across scales. We demonstrate efficient mapping of energy landscapes, correct representation of multiscale hierarchies and transition states, accurate inference of stationary probabilities and transition kinetics, as well as de novo identification of underlying slow, intermediate, and fast reaction coordinates. mMSMs reveal how dynamic processes at different scales contribute collectively to the functional mechanisms of biomolecular machines. Availability and implementation Python code and instructions are available at https://github.com/ravehlab/mMSM. [ABSTRACT FROM AUTHOR]
Copyright of Bioinformatics is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Datenbank: Complementary Index
Beschreibung
Abstract:Motivation Biomolecules undergo dynamic transitions among metastable states to carry out their biological functions. Markov State Models (MSMs) effectively capture these metastable states and transitions at a defined temporal scale. However, biomolecular dynamics typically span multiple temporal scales, ranging from fast atomic vibrations to slower conformational changes and folding events. Results We introduce multiscale Markov State Models (mMSMs), which capture biomolecular dynamics across multiple temporal resolutions simultaneously via a hierarchy of MSMs, and mMSM-explore, an unsupervised algorithm for generating mMSMs through multiscale adaptive sampling with on-the-fly identification of temporally metastable states. We benchmark our method on a toy system with nested energy minima; on alanine dipeptide, first with and then without assuming prior knowledge of its two reaction coordinates; and finally, on a fast-folding 35-residue miniprotein, where we map folding pathways across scales. We demonstrate efficient mapping of energy landscapes, correct representation of multiscale hierarchies and transition states, accurate inference of stationary probabilities and transition kinetics, as well as de novo identification of underlying slow, intermediate, and fast reaction coordinates. mMSMs reveal how dynamic processes at different scales contribute collectively to the functional mechanisms of biomolecular machines. Availability and implementation Python code and instructions are available at https://github.com/ravehlab/mMSM. [ABSTRACT FROM AUTHOR]
ISSN:13674803
DOI:10.1093/bioinformatics/btaf585