Research in this laboratory is centered around solution studies on the structure and dynamics of proteins, protein-protein complexes and protein-nucleic acid complexes using multidimensional NMR spectroscopy, and on the development and application of novel NMR and computational methods to aid in these studies. We have devoted significant efforts towards detecting, characterizing and visualizing highly transient, sparsely-populated states that are invisible to conventional biophysical and structural techniques, yet play a key role in numerous biological processes including recognition, allostery, signal transduction, etc.... by means of paramagnetic relaxation enhancement (PRE) and novel relaxation methods, including Dark state exchange saturation transfer spectroscopy recently developed in our laboratory. Using these approaches we have been able to characterize sliding and hopping of a multidomain transcription factor on DNA, to characteristize the mechanistic details involving encounter complex formation in protein-protein interactions, to study the exchange between monomeric and protofibril forms of amyloid Abeta, and to investigate the interactions of proteins and intrinsically disordered polypeptides with the chaperonin GroEL (including the demonstration that apo GroEL catalyzes the partial unfolding of protein domains and stabilizes the partially folded state relative to both folded and unfolded states of the protein). We have also developed new NMR based methods to study the interactions of proteins with nanoparticles up to 100 nm in diameter. In parallel to our NMR work we have made several developed in pulsed Q-band EPR spectroscopy, including new approaches to measure distances between spin labels up to 160 , the development of IM-DEER to characterize multimeric states of proteins and equilibria between different multimeric states. USing pulsed Q-band EPR measurements we were also able to characterize different conformational states of the finger and thumb subdomains of the p66 subunit in intact HIV-1 reverse transcriptase.
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