Advances in the Treatment of Explicit Water Molecules in Docking and Binding Free Energy Calculations

doi:10.2174/0929867325666180514110824
摘要

背景：在配体受体识别过程中水介导的直接作用是现代计算化学应用于药物发现和开发的热门话题。尽管在过去的几年中已经提出了成功的案例，但仍需要对接或通过显着水合进行虚拟筛查。实际上，如何选择将包含在对接过程中的水分子或应如何处理所包含的水仍然是悬而未决的问题。目的：在这篇综述中，我们将讨论需要明确考虑单一水或相互作用水的小网络影响时可用于计算药物发现和药物开发的一些最新方法。结果：在这里，我们分析软件以帮助选择或预测水分子的位置，这些水分子将在以后的对接研究中明确考虑。我们还将介绍能够在对接过程中有效处理柔性水分子的软件和协议，包括应用示例。最后，我们讨论基于分子动力学模拟的方法，该方法可用于整合对接研究或可靠和有效地计算存在界面或桥联水分子时配体的结合能。结论：协助开发利用水分子的新药物的软件应用正在不断开发，这些药物可作为可置换残基或与受体的桥梁。尽管需要进一步的验证，但是明确考虑水的工作流程可能很快将成为计算药物发现的标准。
关键词: MM-GBSA，MM-PBSA，药物设计，评分，溶剂化，虚拟筛选。
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DOI https://dx.doi.org/10.2174/0929867325666180514110824	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
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