Best Practices for Alchemical Free Energy Calculations [Article v1.0]
Best Practices for Alchemical Free Energy Calculations [Article v1.0]
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DOI：
10.33011/livecoms.2.1.18378
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Mey AS;Allen BK;Macdonald HE;Chodera JD;Hahn DF;Kuhn M;Michel J;Mobley DL;Naden LN;Prasad S;Rizzi A;Scheen J;Shirts MR;Tresadern G;Xu H
炼金术的自由能计算是预测分子从一个环境转移到另一个环境的自由能差异的有用工具。这些方法的特点是使用“桥接”势能函数，代表不能作为真实的化学物种存在的炼金术中间状态。从这些桥接炼金术热力学状态收集的数据允许有效计算转移自由能（或转移自由能的差异），其模拟时间比直接模拟转移过程少几个数量级。虽然这些方法非常灵活，但必须小心避免常见的陷阱，以确保计算的自由能差对于所选力场是鲁棒的和可再现的，并且包括适当的校正以允许与实验数据直接比较。在本文中，我们回顾了目前的最佳做法，几个流行的应用领域的炼金术自由能计算进行平衡模拟，特别是相对和绝对的小分子结合自由能计算生物分子的目标。
Alchemical free energy calculations are a useful tool for predicting free energy differences associated with the transfer of molecules from one environment to another. The hallmark of these methods is the use of “bridging” potential energy functions representing alchemical intermediate states that cannot exist as real chemical species. The data collected from these bridging alchemical thermodynamic states allows the efficient computation of transfer free energies (or differences in transfer free energies) with orders of magnitude less simulation time than simulating the transfer process directly. While these methods are highly flexible, care must be taken in avoiding common pitfalls to ensure that computed free energy differences can be robust and reproducible for the chosen force field, and that appropriate corrections are included to permit direct comparison with experimental data. In this paper, we review current best practices for several popular application domains of alchemical free energy calculations performed with equilibrium simulations, in particular relative and absolute small molecule binding free energy calculations to biomolecular targets.