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G protein–coupled receptors (GPCRs) are versatile molecular machines that regulate the majority of physiological responses to chemically diverse hormones and neurotransmitters. Recent breakthroughs in structural studies have advanced our understanding of GPCR signaling, particularly the selectivity of ligand recognition and receptor activation of G proteins.
Defining G protein–coupled receptor ligand efficacy and biased agonism in precise chemical terms is one challenge posed by the current structural data that exists for this receptor family. Concepts classically used for understanding enzymes and other nonreceptor proteins may lead us in the right direction.