Virtual Substitution Scan Via Single-Step Free Energy Perturbation
Publication in refereed journal

香港中文大學研究人員

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其它資訊
摘要With the rapid expansion of our computing power, molecular dynamics (MD) simulations ranging from hundreds of nanoseconds to microseconds or even milliseconds have become increasingly common. The majority of these long trajectories are obtained from plain (vanilla) MD simulations, where no enhanced sampling or free energy calculation method is employed. To promote the "recycling" of these trajectories, we developed the Virtual Substitution Scan (VSS) toolkit as a plugin of the open-source visualization and analysis software VMD. Based on the single-step free energy perturbation (sFEP) method, VSS enables the user to post-process a vanilla MD trajectory for a fast free energy scan of substituting aryl hydrogens by small functional groups. Dihedrals of the functional groups are sampled explicitly in VSS, which improves the performance of the calculation and is found particularly important for certain groups. As a proof-of-concept demonstration, we employ VSS to compute the solvation free energy change upon substituting the hydrogen of a benzene molecule by 12 small functional groups frequently considered in lead optimization. Additionally, VSS is used to compute the relative binding free energy of four selected ligands of the T4 lysozyme. Overall, the computational cost of VSS is only a fraction of the corresponding multi-step FEP (mFEP) calculation, while its results agree reasonably well with those of mFEP, indicating that VSS offers a promising tool for rapid free energy scan of small functional group substitutions. (C) 2016 Wiley Periodicals, Inc.
著者Chiang YC, Wang Y
期刊名稱Biopolymers
出版年份2016
月份6
日期1
卷號105
期次6
出版社WILEY-BLACKWELL
頁次324 - 336
國際標準期刊號0006-3525
電子國際標準期刊號1097-0282
語言英式英語
關鍵詞free energy calculation; lead optimization; molecular dynamics; single step FEP
Web of Science 學科類別Biochemistry & Molecular Biology; Biophysics

上次更新時間 2020-25-10 於 01:54