The Quantitative Characterization of Functional Allosteric Effects

Seven-transmembrane receptors (7TMRs or GPCRs [G protein–coupled receptors]) are nature's prototypic allosteric proteins in that they mediate the interaction between ligand binding to the receptor and the receptor interacting with another cell signaling protein. A growing class of potential drugs acting through 7TMRs are allosteric in nature in that they bind to a separate site on the receptor protein to modify the interactions between the receptor, natural binding/orthosteric ligand, and signaling proteins. Two main allosteric compound categories are those that increase (positive allosteric modulators [PAMs]) and those that decrease (negative allosteric modulators [NAMs]) receptor-mediated responses. Described in this overview are the molecular parameters used to measure and quantify the interaction of PAMs and NAMs with GPCRs. © 2017 by John Wiley & Sons, Inc.