Cambridge Crystallographic Data Centre, Cambridge, United Kingdom.
Cambridge Crystallographic Data Centre, Cambridge, United Kingdom.
Prog Med Chem. 2021;60:273-343. doi: 10.1016/bs.pmch.2021.01.004. Epub 2021 May 27.
Molecular docking has become an important component of the drug discovery process. Since first being developed in the 1980s, advancements in the power of computer hardware and the increasing number of and ease of access to small molecule and protein structures have contributed to the development of improved methods, making docking more popular in both industrial and academic settings. Over the years, the modalities by which docking is used to assist the different tasks of drug discovery have changed. Although initially developed and used as a standalone method, docking is now mostly employed in combination with other computational approaches within integrated workflows. Despite its invaluable contribution to the drug discovery process, molecular docking is still far from perfect. In this chapter we will provide an introduction to molecular docking and to the different docking procedures with a focus on several considerations and protocols, including protonation states, active site waters and consensus, that can greatly improve the docking results.
分子对接已经成为药物发现过程的重要组成部分。自 20 世纪 80 年代首次开发以来，计算机硬件功能的进步以及小分子和蛋白质结构的数量和可访问性的增加，推动了改进方法的发展，使得对接在工业和学术环境中更加流行。多年来，对接用于辅助药物发现的不同任务的方式发生了变化。尽管最初是作为一种独立的方法开发和使用的，但对接现在主要与集成工作流程中的其他计算方法结合使用。尽管分子对接对药物发现过程做出了宝贵的贡献，但它远非完美。在本章中，我们将介绍分子对接以及不同的对接程序，重点介绍一些可以极大地提高对接结果的注意事项和协议，包括质子化状态、活性位点水和共识。
