In recent years, calculations of binding affinities from molecular simulations seem to have matured significantly. While the number of applications of such methods in drug design and biotechnology increases, the number of truly new methodological developments decreases. This review provides an overview of the current status of the field as reflected in recent publications. The focus is on the challenges that remain when using endstate, alchemical and pathway methods. For endstate methods this is the calculation of entropic contributions. For alchemical methods there are unsolved problems associated with the solvation of the active site, sampling slow degrees of freedom and when modifying the net charge. For pathway methods achieving sufficient sampling remains challenging. New trends are also highlighted, including the use of pathway methods for the quantification of protein-protein interactions.

中文翻译：

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结合自由能的计算进展。

近年来，通过分子模拟计算的结合亲和力似乎已经大大成熟。尽管此类方法在药物设计和生物技术中的应用数量增加了，但真正的新方法学开发的数量却在减少。这篇综述概述了最新出版物中反映的该领域的当前状况。重点是使用最终状态，炼金术和途径方法时仍然存在的挑战。对于最终状态方法，这是熵贡献的计算。对于炼金方法，存在与活性位点的溶剂化，缓慢的自由度采样以及修改净电荷有关的未解决的问题。对于途径方法，实现足够的采样仍然具有挑战性。还强调了新趋势，