Site-Selective Gaussian Accelerated Molecular Dynamics and Its Integration with Replica-Exchange Methods
- 1Graduate School of Science, University of Hyogo, 3-2-1 Koto, Kamigori-cho, Ako-gun, Hyogo, 678-1297
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.
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BibTeX
@misc{oshima2026siteselective,
title = {{Site-Selective Gaussian Accelerated Molecular Dynamics and Its Integration with Replica-Exchange Methods}},
author = {Hiraku Oshima},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010586/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010586/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Site-Selective Gaussian Accelerated Molecular Dynamics and Its Integration with Replica-Exchange Methods
AU - Hiraku Oshima
PY - 2026
DA - 2026/10/16
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010586/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010586/v1
AB - 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.
ER -