论文标题

炼金术自由能计算的最佳实践

Best Practices for Alchemical Free Energy Calculations

论文作者

Mey, Antonia S. J. S., Allen, Bryce, Macdonald, Hannah E. Bruce, Chodera, John D., Kuhn, Maximilian, Michel, Julien, Mobley, David L., Naden, Levi N., Prasad, Samarjeet, Rizzi, Andrea, Scheen, Jenke, Shirts, Michael R., Tresadern, Gary, Xu, Huafeng

论文摘要

炼金术自由能计算是预测与分子从一个环境转移到另一种环境的转移相关的自由能差的有用工具。这些方法的标志是使用代表\ emph {炼金术}中间状态的“桥接”势能函数,这些状态不能作为真实的化学物质存在。从这些桥接炼金术热力学状态收集的数据允许有效地计算传递自由能(或传递自由能中的差异),其模拟时间比直接模拟传输过程要少。尽管这些方法非常灵活,但必须注意避免常见的陷阱,以确保所选力场计算的自由能差可以鲁棒且可重复,并且包括适当的校正以允许直接与实验数据进行比较。在本文中,我们回顾了炼金术自由能计算的几个流行应用领域的当前最佳实践,包括相对和绝对的小分子结合能量与生物分子靶标。

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 \emph{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, including relative and absolute small molecule binding free energy calculations to biomolecular targets.

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