Grinter Sam Z, Zou Xiaoqin
Informatics Institute, University of Missouri, Columbia, MO 65211, USA.
Molecules. 2014 Jul 11;19(7):10150-76. doi: 10.3390/molecules190710150.
The docking methods used in structure-based virtual database screening offer the ability to quickly and cheaply estimate the affinity and binding mode of a ligand for the protein receptor of interest, such as a drug target. These methods can be used to enrich a database of compounds, so that more compounds that are subsequently experimentally tested are found to be pharmaceutically interesting. In addition, like all virtual screening methods used for drug design, structure-based virtual screening can focus on curated libraries of synthesizable compounds, helping to reduce the expense of subsequent experimental verification. In this review, we introduce the protein-ligand docking methods used for structure-based drug design and other biological applications. We discuss the fundamental challenges facing these methods and some of the current methodological topics of interest. We also discuss the main approaches for applying protein-ligand docking methods. We end with a discussion of the challenging aspects of evaluating or benchmarking the accuracy of docking methods for their improvement, and discuss future directions.
基于结构的虚拟数据库筛选中使用的对接方法能够快速且低成本地估计配体与目标蛋白受体（如药物靶点）的亲和力和结合模式。这些方法可用于富集化合物数据库，从而使后续经实验测试的更多化合物被发现具有药学价值。此外，与用于药物设计的所有虚拟筛选方法一样，基于结构的虚拟筛选可以专注于可合成化合物的精选文库，有助于降低后续实验验证的成本。在本综述中，我们介绍了用于基于结构的药物设计和其他生物学应用的蛋白质-配体对接方法。我们讨论了这些方法面临的基本挑战以及当前一些感兴趣的方法学主题。我们还讨论了应用蛋白质-配体对接方法的主要途径。最后，我们讨论了评估或基准测试对接方法准确性以促进其改进方面的挑战性问题，并探讨了未来的方向。
