Abstract：
G protein-coupled receptors (GPCRs) play a key role in the transduction of extracellular signals to cells and regulation of many biological processes, which makes these membrane proteins one of the most important targets for pharmacological agents. A significant increase in the number of resolved atomic structures of GPCRs has opened the possibility of developing pharmaceuticals targeting these receptors via structure-based drug design (SBDD). SBDD employs information on the structure of receptor-ligand complexes to search for selective ligands without the need for an extensive high-throughput experimental ligand screening and can significantly expand the chemical space for ligand search. In this review, we describe the process of deciphering GPCR structures using X-ray diffraction analysis and cryoelectron microscopy as an important stage in the rational design of drugs targeting this receptor class. Our main goal was to present modern developments and key features of experimental methods used in SBDD of GPCR-targeting agents to a wide range of specialists.
摘要：
G蛋白偶联受体(GPCRs)在细胞外信号的转导和许多生物过程的调节中起着关键作用,这使得这些膜蛋白成为药物最重要的靶标之一。GPCRs的分辨原子结构的数量的显著增加开启了通过基于结构的药物设计(SBDD)开发靶向这些受体的药物的可能性。SBDD利用有关受体-配体复合物结构的信息来搜索选择性配体，而无需进行广泛的高通量实验配体筛选，并且可以显着扩展用于配体搜索的化学空间。在这次审查中,我们描述了使用X射线衍射分析和低温电子显微镜破译GPCR结构的过程，这是合理设计针对该受体类别的药物的重要阶段。我们的主要目标是向广泛的专家介绍GPCR靶向剂SBDD中使用的实验方法的现代发展和关键特征。
