Department of Physics and Astronomy
Kinard G01, Lecture Hall
Thursday, March 13, 4:00 pm
Dr. Huan-Xiang Zhou
Department of Physics and Institute of Molecular Biophysics
Florida State University, Tallahassee, FL
Protein Association in Dilute and Crowded Solutions
Abstract: Most biological processes are mediated by protein association, which is often under kinetic rather than thermodynamic control. We have developed the transient-complex theory for protein association, which presents a framework for elucidating the mechanisms of protein association and for predicting the association rate constants. The transient complex refers to an intermediate along the association process, in which the two associating molecules have near-native separation and relative orientation but have yet to form the short-range specific interactions of the native complex. Our theory rationalizes the variations in association rate constants over 10 orders of magnitude and its computational implementation gives accurate prediction of the rate constants based on the structures of the native complexes. We find that disordered proteins bind to their targets often via a dock-and-coalesce mechanism, whereby a segment of the disordered protein first docks to its cognate subsite and the remaining segments subsequently explore conformational space and coalesce around their cognate subsites. We propose that intrinsic disorder allows proteins to form complexes that are highly specific and yet short-lived, twin requirements for signaling and regulatory purposes. In the cellular context, association processes occur in the presence of a high concentration of bystander macromolecules. We have developed methods to model the effects of the crowded cellular environments on the affinities and rate constants of protein association. These studies allow us to achieve a quantitative understanding of biological processes in the cellular context, based on physical principles.
Bio Sketch: Dr. Huan-Xiang Zhou received his PhD from Drexel University in 1988, and did postdoctoral work at the NIH. After faculty appointments at HKUST and Drexel, he moved in 2002 to Florida State University, where he is now Distinguished Research Professor. His group does theoretical, computational, and experimental research on protein association, crowding and confinement effects of cellular environments, functional mechanisms of ion channels, and self-assembly of peptides. He is an elected fellow of the AAAS and of the APS. He has published over 200 papers and has an H-index of 46.
Refreshments will be served afterward in the PandA café on the 1st floor of Kinard Lab.
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