Solute Tempered Adiabatic Free Energy Dynamics for Enhancing Conformational Space Sampling.

Authors

Shitanshu Bajpai, Charlles R A Abreu, Nisanth N Nair, Mark E Tuckerman

Published in

Journal of chemical theory and computation. Jun 05, 2025. Epub Jun 05, 2025.

Abstract

Collective variable (CV) and generalized ensemble-based enhanced sampling methods are widely used for accelerating barrier-crossing events and enhancing conformational sampling in molecular dynamics simulations. Temperature-accelerated molecular dynamics (TAMD)/driven-adiabatic free energy dynamics (d-AFED) uses extended variables thermostated at high temperature to achieve better exploration of conformational space. Replica exchange with solute tempering (REST2) achieves improved sampling by scaling the solute-solute and solute-solvent interaction energies of different replicas and swapping conformations between them. It has been observed that a combination of CV-based enhanced sampling and global tempering is needed to boost the conformational sampling of large biomolecular systems due to the presence of large entropic basins. In this work, we propose a method called "Solute Tempered d-AFED" or "STed-AFED" that combines both d-AFED/TAMD and REST2. We implemented this approach in the OpenMM-UFEDMM interface and demonstrated the efficiency of this method by studying the conformational landscapes of small peptides and proteins, in particular, chignolin, Trp-cage, and villin.

PMID:
40472259
Bibliographic data and abstract were imported from PubMed on 06 Jun 2025.

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