Seminar: Mapping allosteric regulation of membrane proteins in signaling, transport and drug discovery

Membrane proteins must transition among multiple conformational states to perform their diverse functions. Various classes of membrane-bound receptors adopt intermediate states that regulate activation kinetics, recognize particular binding partners or render a protein susceptible to modulation by small-molecule ligands; but these crucial states are often challenging to detect due to their transient nature. 

Here, I describe integrated computational and experimental biophysical strategies to illuminate conformational states, and to capture transitions between states, that together define the energy landscapes of G-protein coupled receptors (GPCRs) and other membrane proteins. Through these conformational "movies," I determine mechanisms of allostery and conformational change in various classes of membrane-bound receptors, providing atomic-level insights that may aid in the design of new GPCR-targeted ligands in drug discovery.