G protein-coupled receptors (GPCRs) translate binding of extracellular ligands into intracellular responses through conformational changes. Ligand properties are described by the maximum response (efficacy) and the agonist concentration at half-maximal response (potency). Integrating structural changes with pharmacological properties remains challenging and has not yet been performed at the resolution of individual amino acids. We use epinephrine and β2-adrenergic receptor as a model to integrate residue-level pharmacology data with intramolecular residue contact data describing receptor activation. This unveils the allosteric networks driving ligand efficacy and potency. We provide detailed insights into how structural rearrangements are linked to fundamental pharmacological properties at single-residue level in a receptor-ligand system. Our approach can be used to determine such pharmacological networks for any receptor-ligand complex.

中文翻译：

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剖析控制 G 蛋白偶联受体激动剂功效和效力的变构网络

G 蛋白偶联受体 (GPCR) 通过构象变化将细胞外配体的结合转化为细胞内反应。配体特性由最大响应（效力）和半最大响应时的激动剂浓度（效力）描述。将结构变化与药理特性相结合仍然具有挑战性，并且尚未在单个氨基酸的分辨率下进行。我们使用肾上腺素和 β2-肾上腺素能受体作为模型，将残留水平的药理学数据与描述受体激活的分子内残留接触数据相结合。这揭示了驱动配体功效和效力的变构网络。我们提供了关于结构重排如何与受体-配体系统中单残基水平的基本药理特性相关的详细见解。