Demand for novel GPCR modulators is increasing as the association between the GPCR signaling pathway and numerous diseases such as cancers, psychological and metabolic disorders continues to be established. In silico structure-based drug design (SBDD) offers an outlet where researchers could exploit the accumulating structural information of GPCR to expedite the process of drug discovery. The coupling of structure-based approaches such as virtual screening and molecular docking with molecular dynamics and/or Monte Carlo simulation aids in reflecting the dynamics of proteins in nature into previously static docking studies, thus enhancing the accuracy of rationally designed ligands. This review will highlight recent computational strategies that incorporate protein flexibility into SBDD of GPCR-targeted ligands.

中文翻译：

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蛋白质动力学在AG类蛋白质偶联受体（GPCR）的基于结构的药物发现中的重要性。

随着GPCR信号通路与众多疾病（例如癌症，心理疾病和代谢紊乱）之间的联系不断建立，对新型GPCR调节剂的需求正在增加。在计算机模拟中，基于结构的药物设计（SBDD）提供了一个渠道，研究人员可以利用该渠道利用GPCR积累的结构信息来加快药物发现的过程。虚拟筛选和分子对接等基于结构的方法与分子动力学和/或蒙特卡洛模拟的结合，有助于将自然界中蛋白质的动力学反映到以前的静态对接研究中，从而提高了合理设计配体的准确性。这篇综述将重点介绍将蛋白质灵活性纳入GPCR靶向配体的SBDD的最新计算策略。