Watching molecular recognition of drugs by their biological receptors one molecule at a time

ANYL 228

Mary J. Wirth, mwirth@email.arizona.edu1, Takahira Tokimoto1, Tomika Bethea1, and John S. Kirk, john-kirk@uiowa.edu2. (1) Department of Chemistry, University of Arizona, 1306 E. University Blvd., Tucson, AZ 85721, (2) Department of Chemistry, University of Iowa, 313 CB, Iowa City, IA 52242
Among the many phenomena in chemical biology that has eluded informative measurement is the recognition of drugs by their biological receptors. G-protein coupled receptors are the targets of most pharmaceuticals, yet they are not amenable to protein crystallography. Drug design would be greatly facilitated by a molecular level understanding of how drugs bind to the receptor, and how a bound drug then chaperones the receptor into its biologically active conformation. Single-molecule spectroscopy has the potential to lend enormous molecular insight into this complex process, reporting on the kinetics of binding, the kinetics of receptor conformational change, the synchrony of drug and G-protein binding, the orientations of a dye label bound to the drug, and the behaviors of different classes of drugs, including agonists, antagonists and inverse agonists. Single-molecule spectroscopy is well suited to the study of the heterogeneous and dynamic phenomenon of binding and activation of G-protein coupled receptors.