{"title":"Enhanced Sampling with Suboptimal Collective Variables: Reconciling Accuracy and Convergence Speed.","authors":"Dhiman Ray, Valerio Rizzi","doi":"10.1021/acs.jctc.4c01231","DOIUrl":null,"url":null,"abstract":"<p><p>We introduce an enhanced sampling algorithm to obtain converged free energy landscapes of molecular rare events, even when the collective variable (CV) used for biasing is not optimal. Our approach samples a time-dependent target distribution by combining the on-the-fly probability enhanced sampling and its exploratory variant, OPES Explore. This promotes more transitions between the relevant metastable states and accelerates the convergence speed of the free energy estimate. We demonstrate the successful application of this combined algorithm on the two-dimensional Wolfe-Quapp potential, millisecond time-scale ligand-receptor binding in the trypsin-benzamidine complex, and folding-unfolding transitions in chignolin mini-protein. Our proposed algorithm can compute accurate free energies at an affordable computational cost and is robust in terms of the choice of CVs, making it particularly promising for the simulation of complex biomolecular systems.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"58-69"},"PeriodicalIF":5.7000,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Theory and Computation","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.jctc.4c01231","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
We introduce an enhanced sampling algorithm to obtain converged free energy landscapes of molecular rare events, even when the collective variable (CV) used for biasing is not optimal. Our approach samples a time-dependent target distribution by combining the on-the-fly probability enhanced sampling and its exploratory variant, OPES Explore. This promotes more transitions between the relevant metastable states and accelerates the convergence speed of the free energy estimate. We demonstrate the successful application of this combined algorithm on the two-dimensional Wolfe-Quapp potential, millisecond time-scale ligand-receptor binding in the trypsin-benzamidine complex, and folding-unfolding transitions in chignolin mini-protein. Our proposed algorithm can compute accurate free energies at an affordable computational cost and is robust in terms of the choice of CVs, making it particularly promising for the simulation of complex biomolecular systems.
期刊介绍：
The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.
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