Drug-receptor dynamics designates the time-dependent behaviour of drug–receptor interactions, encompassing the kinetics of ligand association and dissociation and the conformational transitions through which receptors and ligand–receptor complexes interconvert among functional states. The elementary kinetic scheme describes a reversible bimolecular reaction in which a drug combines with a free receptor at an association rate constant (kon) to form a drug–receptor complex and dissociates at a dissociation rate constant (koff), with the equilibrium dissociation constant KD defined as the ratio koff/kon and serving as the quantitative measure of binding affinity [1]. The reciprocal of koff defines the residence time of the complex, a parameter that has been recognized as a determinant of therapeutic efficacy and safety that is not captured by equilibrium affinity alone [2][3]. A defining feature of drug-receptor dynamics is the dynamic character of the receptor itself: receptors are flexible entities that sample multiple conformational states, and the binding of orthosteric or allosteric ligands modulates these conformational dynamics to elicit distinct functional responses, including full, partial, inverse, and biased agonism [4][5]. The term thus denotes the kinetic and conformational description of drug–receptor systems—spanning rate constants, residence time, and state-dependent receptor transitions—as the mechanistic basis for the intensity, duration, and selectivity of drug action [2][4][6].
- Association rate constant
- dissociation rate constant
- residence time
- conformational dynamics
- biased agonism
References
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- Paolo Conflitti; Edward Lyman; Mark S. P. Sansom; Peter W. Hildebrand; Hugo Gutiérrez-De-Terán; Paolo Carloni; T. Bertie Ansell; Shuguang Yuan; Patrick Barth; Anne S. Robinson; et al. Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery. Nat. Rev. Drug Discov. 2025, 24, 251-275, 10.1038/s41573-024-01083-3.
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- Robert A Copeland; The dynamics of drug-target interactions: drug-target residence time and its impact on efficacy and safety. Expert Opin. Drug Discov. 2010, 5, 305-310, 10.1517/17460441003677725.