Multiple active receptor conformation, agonist efficacy and maximum effect of the system: the conformation-based operational model of agonism

► The operational model is extended by including a ligand-induced receptor conformation. ► It is proposed that the system maximum effect depends on receptor conformation. ► The model links receptor active conformations to agonist affinity and efficacy. ► The model can explain the activity of superagonists and allosteric modulators.