G protein-coupled receptors (GPCRs) are particularly attractive targets for therapeutic pharmaceuticals. This is because they are involved in almost all facets of physiology, in many pathophysiological processes, they are tractable due to their cell surface location, and can exhibit highly textured pharmacology. While the development of new drugs does not require the molecular details of the mechanism of activity for a particular target, there has been increasing interest in the GPCR field in these details. In part, this has come with the recognition that differential activity at a particular target might be a way in which to leverage drug activity, either through manipulation of efficacy or through differential coupling (signaling bias). To this end, the past few years have seen a number of publications that have specifically attempted to address one or more aspects of the molecular reaction pathway, leading to activation of heterotrimeric G proteins by GPCRs.

中文翻译：

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G蛋白偶联受体的构象转变和异三聚体G蛋白的活化。

G蛋白偶联受体（GPCR）是治疗药物特别有吸引力的靶标。这是因为它们在许多病理生理学过程中几乎涉及生理学的所有方面，由于它们在细胞表面的位置而易于处理，并且可以表现出高度织构的药理学。尽管新药的开发不需要特定靶标的活性机制的分子细节，但在GPCR领域中，人们对这些细节的兴趣日益浓厚。在某种程度上，这已经认识到，在特定目标上的差异活性可能是通过功效控制或差异偶联（信号偏倚）来利用药物活性的一种方式。为此，