Conformational flexibility and dynamics underlie the most essential property that makes proteins unique molecular machines. The objective of this research is to develop general analytic and computational approaches to characterize mechanisms controlling conformational transitions involving flexible proteins. This research focuses on two important classes of conformational transitions: (a) allosteric transitions between two distinct conformational ensembles; and (b) coupled folding and binding. A central issue uniting these two different kinds of transitions is the role that flexibility has in reducing free energy barriers and enhancing transition rates. For both kinds of transitions, the structural and spatial properties of transition state ensembles will be characterized at the residue level resolution. This allows identification of kinetically important residues controlling conformational transitions. The analytic theory and simulations developed in this research are complementary: the simulations will help evaluate ideas and predictions obtained from the analytic model, and the natural structural parameters of the analytic model will influence how the simulated trajectories are analyzed.
Educational goals center around increasing exposure of undergraduate students to interdisciplinary research areas. This includes continued development of an undergraduate biological physics course which gives students experience and familiarity with interdisciplinary topics otherwise lacking in our physics curriculum. This project also provides an opportunity of early research experience for undergraduate students. This opportunity complements two funded scholarship programs at KSU aimed at recruitment, retention, and support of science students to ensure a successful transition into scientific or high-technology careers. Lastly, this project will guide development of computer learning modules aimed at helping undergraduate students in chemistry, material science, biology, and physics connect molecular-level physical concepts with macroscopic observations.
