Site-Selective Gaussian Accelerated Molecular Dynamics and Its Integration with Replica-Exchange Methods
Year: 2026
Type: preprint
Abstract: We developed site-selective Gaussian accelerated molecular dynamics (ssGaMD), which selectively enhances molecular motions associated with a specified region or set of interactions. The method allows selected dihedral, electrostatic, and Lennard–Jones energy terms to be biased independently or in combination, while limiting direct biasing of the rest of the system. ssGaMD can be combined with replica-exchange umbrella sampling (ssGaREUS) or temperature replicaexchange molecular dynamics (ssGaREMD) to further enhance the sampling of association and dissociation processes and conformational changes. We implemented these methods in the GENESIS MD simulation software and applied them to aspirin binding to β-cyclodextrin, PP1 binding to Src kinase, and Trp-cage folding. Selectively boosting interactions involved in binding efficiently promoted molecular association and dissociation, while combining ssGaMD with replica-exchange methods accelerated the convergence of binding and folding free-energy landscapes. These methods offer a flexible approach to studying ligand binding and other biomolecular processes in which slow dynamics are governed by specific local interactions.
Source: ChemRxiv
Author: Hiraku Oshima
Institution: University of Hyogo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7222590329