Revealing the Atomistic Mechanism of Rare Events in Molecular Dynamics

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Authors: Jakob J. Kresse, Alexander Sikorski, Vikram Sunkara, Surahit Chewle, Marcus J. Weber
Cited by: 1
References: 42

Abstract

Interpretable reaction coordinates are essential for understanding rare conformational transitions in molecular dynamics. The Atomistic Mechanism of Rare Events in Molecular Dynamics (AMORE-MD) framework enhances the interpretability of deep-learned reaction coordinates by connecting them to atomistic mechanisms, without requiring any a priori knowledge of collective variables, pathways, or end points. Here, AMORE-MD employs the ISOKANN algorithm to learn a neural membership function χ representing the dominant slow process, from which transition pathways are reconstructed as minimum-energy paths aligned with the gradient of χ, and atomic contributions are quantified through gradient-based sensitivity analysis. Iterative enhanced sampling further enriches transition regions and improves coverage of rare events, enabling recovery of known mechanisms and chemically interpretable structural rearrangements at atomic resolution for the Müller-Brown potential, alanine dipeptide, and the elastin-derived hexapeptide VGVAPG.

Fields of Study & Subjects

Advanced Physical and Chemical Molecular Interactions Protein Structure and Dynamics Origins and Evolution of Life

Publication details

Journal / source
Journal of Chemical Theory and Computation
Publisher
American Chemical Society (ACS)
Volume
22
Issue
5
Pages
2380–2389
Publication date
23 February 2026
Language
EN