Revealing the Atomistic Mechanism of Rare Events in Molecular Dynamics
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