G-protein-coupled receptors (GPCRs) are allosteric signaling machines that trigger distinct functional responses depending on the particular conformational state they adopt upon binding. This so-called GPCR functional selectivity is prompted by ligands of different efficacy binding at orthosteric or allosteric sites on the receptor, as well as by interactions with intracellular protein partners or other receptor types. Molecular dynamics (MD) simulations can provide important mechanistic, thermodynamic, and kinetic insights into these interactions at a level of molecular detail that is necessary to rightly inform modern drug discovery. Here, we review the most recent MD contributions to understanding GPCR allostery, with an emphasis on their strengths and limitations.

中文翻译：

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通过分子动力学模拟研究了G蛋白偶联受体的变构。

G蛋白偶联受体（GPCR）是一种变构信号转导机器，其根据结合时所采用的特定构象状态触发不同的功能响应。所谓的GPCR功能选择性是由受体的正构或变构位点结合不同功效的配体以及与细胞内蛋白伴侣或其他受体类型的相互作用所引起的。分子动力学（MD）模拟可以在分子详细程度为这些相互作用提供重要的机理，热力学和动力学方面的见解，这是正确告知现代药物发现所必需的。在这里，我们回顾了最新的医学博士对理解GPCR变构的贡献，重点是它们的优势和局限性。