ABSTRACT
Since the Monod-Wyman-Changeux (MWC) model was initially proposed to explain the allosteric interactions between proteins and their ligands 50 years ago, there have been various models and hypotheses such as the induced-fit model on the interaction. These theoretical developments have been used broadly in the study of allosteric modulations of enzymes and receptors. In 1980, Lefkowitz and coworkers proposed a ternary complex model (TCM) for the regulatory mechanism of G protein-coupled receptors (GPCRs) that laid the theoretical foundation in the study of allosteric sites and ligands of GPCRs, the largest family of known receptors. The findings on how ligands interact with receptors to cause a functional response have significantly impacted the drug discovery field and accelerated the identification of allosteric modulators.