Flexibility of proteins is an integral part of their function. This motion can include reorganization of catalytic groups, loop closures, and domain movement, to name a few. The focus of our research is to understand how the dynamic and structural properties of proteins correlate with their function. The general questions that we would like to address are:

• How do changes in the structure and dynamics of enzymes contribute to catalysis, ligand specificity, and affinity?
• What aspects of the protein's conformational landscape are reshaped via allosteric ligand binding or mutagenesis?

Our primary experimental tool for approaching these questions is nuclear magnetic resonance (NMR) spectroscopy. NMR is the only experimental technique that can access molecular motion on time scales from 10^-12 - 10¹ seconds with atomic resolution.

A detailed understanding of the link between enzyme flexibility and function is crucial for protein engineering, protein and drug design and for obtaining a physical chemical understanding of enzyme function. Our lab utilizes many biophysical techniques with a focus on solution NMR spectroscopy to characterize conformational motions in functional enzymes. We are currently addressing the issues in three distinct areas: (1) We are trying to understand relationship between active site loop motions and their allosteric regulation in protein tyrosine phosphatases. (2) In the enzyme imidazole glycerol phosphate synthase we are searching for a mechanistic understanding of allosteric information transfer that spans tens of Angstroms. (3) Whereas in DNA Polymerase beta (Polb) we are trying to illuminate the role of protein flexibility on substrate fidelity in cancer causing mutants of Polb.