NMR spectroscopy is a powerful approach for probing the conformational dynamics of biological macromolecules, uniquely providing both temporal and atomic resolution. Over the past three decades, NMR spin relaxation investigations in particular have revealed or substantiated biophysical concepts that are critical for specificity and affinity of molecular recognition by proteins and other macromolecules. These insights include the contribution of conformational entropy, the balance between selected- and induced fit mechanisms, the prevalence of coupled folding and binding events, and the roles of sparsely populated conformational states along a reaction coordinate. These concepts will be illustrated by applications to AlkB and ribonuclease H enzymes, the transcription factor GCN4, and classical cadherin cell-cell adhesion molecules. In these applications, use of multiple static magnetic fields, temperature and pressure perturbations, and site-specific mutations are critical for full experimental characterization of dynamics processes and molecular dynamics simulations provide key atomic mechanistic insights. As a consequence of advances in NMR spectroscopy and computational methods, the long-sought goal of understanding "How do proteins work?" increasingly can be answered in spatio-temporal detail.
3:00-4:00 Opportunity for trainees to meet with the Robert Ross speaker
159 Davis Heart and Lung Institute
Refreshments provided