4/25 - Seminar (chem bio): Peter Wright, Scripps Research Institute
Peter Wright - speaker's webpage
Department of Molecular Biology
Scripps Research Institute
Host: Michael Hecht
Exploring protein energy landscapes by NMR relaxation
Molecular motions are central to the biological functions of proteins. NMR provides unique information on dynamic processes, advancing our understanding beyond the level of three-dimensional protein structure to reveal the conformational flexibility and motions that are directly relevant to biological function. NMR relaxation measurements provide a powerful approach for direct experimental characterization of protein dynamics and protein folding processes on a broad range of time scales, ranging from ps to ms. In particular, relaxation dispersion experiments permit quantitative analysis of the dynamics and thermodynamics of slow conformational fluctuations in proteins and allow structural characterization of weakly populated conformational substates. Such experiments support a view of proteins as dynamic conformational ensembles, providing new mechanistic understanding of allostery, molecular recognition, and enzyme catalysis, and new insights into mechanisms of protein folding and misfolding in disease. Applications of NMR relaxation dispersion experiments to characterize the dynamic conformational ensemble of the enzyme dihydrofolate reductase and to elucidate protein folding and unfolding pathways will be described.