■如今,人们普遍认为水分子在配体与分子靶标结合中起关键作用。在分子识别过程中忽略水分子是基于结构的药物发现活动中多次失败的结果。WaterMap的应用,特别是WaterMap引导的分子对接,可以合理准确和快速地描述配体-蛋白质界面处水分子的位置和能量。
■在这篇评论中,作者简要讨论了水在药物设计和发现中的重要性,并简要概述了用于预测溶剂相关效应的计算方法,以便在其他可用技术和工具的背景下介绍WaterMap。在简要描述WaterMap概念之后,介绍了2013年至2023年之间发布的WaterMap辅助虚拟筛选文献。
■近年来,WaterMap软件已广泛用于支持基于结构的药物设计,尤其是基于结构的虚拟筛选。的确,考虑到结合袋中的水分子,它是重新计算对接结果的有用工具。尽管WaterMap允许考虑结合位点中水分子的动态行为,为了获得最佳准确性,建议将其与FEP的MM-GB/SA等其他技术结合使用。
Nowadays, it is widely accepted that water molecules play a key role in binding a ligand to a molecular target. Neglecting water molecules in the process of molecular recognition was the result of several failures of the structure-based drug discovery campaigns. The application of WaterMap, in particular WaterMap-guided molecular docking, enables the reasonably accurate and quick description of the location and energetics of water molecules at the ligand-protein interface.
In this review, the authors shortly discuss the importance of water in drug design and discovery and provide a brief overview of the computational approaches used to predict the solvent-related effects for the purposes of presenting WaterMap in the context of other available techniques and tools. A concise description of WaterMap concept is followed by the presentation of WaterMap-assisted virtual screening literature published between 2013 and 2023.
In recent years, WaterMap software has been extensively used to support structure-based drug design, in particular structure-based virtual screening. Indeed, it is a useful tool to rescore docking results considering water molecules in the binding pocket. Although WaterMap allows for the consideration of the dynamic behavior of water molecules in the binding site, for best accuracy, its application in conjunction with other techniques such as molecular mechanics-generalized Born surface area of FEP (Free Energy Perturbation) is recommended.