Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
Trends Pharmacol Sci. 2012 May;33(5):268-72. doi: 10.1016/j.tips.2012.03.007. Epub 2012 Apr 13.
G-protein-coupled receptors (GPCRs) represent a large family of signaling proteins that includes many therapeutic targets; however, progress in identifying new small molecule drugs has been disappointing. The past 4 years have seen remarkable progress in the structural biology of GPCRs, raising the possibility of applying structure-based approaches to GPCR drug discovery efforts. Of the various structure-based approaches that have been applied to soluble protein targets, such as proteases and kinases, in silico docking is among the most ready applicable to GPCRs. Early studies suggest that GPCR binding pockets are well suited to docking, and docking screens have identified potent and novel compounds for these targets. This review will focus on the current state of in silico docking for GPCRs.
G 蛋白偶联受体（GPCRs）是一大类信号蛋白家族，其中包括许多治疗靶点；然而，在发现新的小分子药物方面的进展却令人失望。在过去的 4 年中，GPCR 的结构生物学取得了显著进展，为应用基于结构的方法进行 GPCR 药物发现提供了可能。在已经应用于可溶性蛋白靶标的各种基于结构的方法中，如蛋白酶和激酶，计算对接是最适合 GPCR 的方法之一。早期研究表明，GPCR 结合口袋非常适合对接，对接筛选已经为这些靶点鉴定了有效和新颖的化合物。本文将重点介绍目前用于 GPCR 的计算对接技术。
