BMMB, CHEM, MCIBS
Biophysical Chemistry applied to solution NMR spectroscopy of partially disordered proteins. NMR studies of protein dynamics coupled with computational and theoretical studies of the coupling between nuclear spin relaxation and molecular motion. Emphasis is placed on biophysical studies of macromolecular interactions involving partially disordered proteins, for the purpose of understanding the functional implications of protein dynamics and disorder in protein mediated signaling and oncogenesis/ tumor suppression.
Dynamics and Disorder in Protein Ligand Interactions
Proteins are dynamic molecules and developing an intuitive understanding of the relationship between structure, dynamics, and function is a universally valuable goal. The primary research tools used by members of our laboratory are Nuclear Magnetic Resonance spectroscopy (NMR), molecular dynamics simulations (MD), and Isothermal Titration Calorimetry (ITC). Since our emphasis is on studying interactions involving disordered proteins and flexible agonists, the focus of the work is on the conformational dynamics of proteins and the contributions of these dynamics to protein-protein interactions. For flexible systems with disorder-order transitions coupled to the binding event, NMR spectroscopy remains the most powerful source of atomic level biophysical information available, with access to dynamics on the fast ps-ns timescale, as well as the biologically critical μs-ms timescale. Shifting focus from backbone to side chain NMR dynamics further broadens the possibilities for understanding protein-protein interactions and non-folded systems. Combined analysis of experimental NMR data and computational results provides a uniquely detailed picture of correlated dynamics. Rigorous protocols for cross validation of MD trajectories and theoretical calculations against diverse experimental NMR data are applied throughout the projects in our laboratory.