Soochow University, Suzhou, Jiangsu, China.
Curr Med Chem. 2010;17(12):1167-80. doi: 10.2174/092986710790827807.
G protein-coupled receptors (GPCRs) mediate senses such as odor, taste, vision, and pain in mammals. In addition, important cell recognition and communication processes often involve GPCRs. Many diseases involve malfunction of GPCRs, making them important targets for drug development. Indeed, greater than 50 % of all marketed therapeutics act on those receptors. Unfortunately, the atomic-level structures are only available for rhodopsin, beta2AR, beta1AR, A2A adenosin and opsin. In silico computational methods, employing receptor-based modeling, offer a rational approach in the design of drugs targeting GPCRs. These approaches can be used to understand receptor selectivity and species specificity of drugs that interact with GPCRs. This review gives an overview of current computational approaches to GPCR model building; ligand-receptor interaction for drug design; and molecular mechanism of GPCR activation from simulation.
G 蛋白偶联受体（GPCRs）介导哺乳动物的嗅觉、味觉、视觉和疼痛等感觉。此外，重要的细胞识别和通讯过程通常涉及 GPCRs。许多疾病涉及 GPCRs 的功能障碍，使其成为药物开发的重要靶点。事实上，超过 50%的上市治疗药物作用于这些受体。不幸的是，只有视紫红质、β2AR、β1AR、A2A 腺苷和视蛋白的原子水平结构可用。基于受体的建模的计算方法为靶向 GPCR 的药物设计提供了一种合理的方法。这些方法可用于了解与 GPCR 相互作用的药物的受体选择性和物种特异性。本文综述了 GPCR 模型构建的当前计算方法；配体-受体相互作用的药物设计；以及 GPCR 激活的分子机制模拟。
