The biological role of structural fluctuations in proteins has not been established although their presence has been amply demonstrated. This is partly due to uncertainty about the thermodynamic basis for the phenomenon. Possibilities range from passage between defined conformational substrates, as in the allosteric model for hemoglobin, to pure kinetic regulation of the passage along the reaction coordinate of enzyme substrate complex. Dr. Rosenberg will base the planned research on a physical model that he has developed for these phenomena. The overall goal will be to test the validity of model and then demonstrate its usefulness in explaining the possible function of structural fluctuations in biological processes. He has selected sound experimental systems using well- characterized proteins and tested analytical methodologies. A major strength of this project is the diversity of methodologies (hydrogen-exchange, fluorescence-quenching, thermal stability) being applied to the study of protein motions.
