Dynamics and flexibility of G-protein-coupled receptor conformations and their relevance to drug design

Abstract

G-protein coupled receptors (GPCRs) are seven helical transmembrane proteins with functional diversity and form the largest superfamily of drug targets. The functional diversity of these receptors stems from the conformational flexibility of the receptor, the nature of the ligand activating the receptor, and the intracellular protein that the receptor couples to. A molecular level understanding of the influence of each of these factors will greatly aid the design of functional selective drugs. In this review, the current state of our understanding of the conformational flexibility and dynamics of class A GPCRs derived from a confluence of biophysical and computational techniques is elucidated.