Teh Pat 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:

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. Historically, detailed NMR studies have been restricted to peptides and small proteins. However recent advances in the field have allowed for in-depth studies of larger proteins, opening up this technique to a broad range of interesting protein dynamics questions.

The fields of drug design, protein engineering, and de novo protein design all require a detailed understanding of the flexibility and three-dimensional structures of the molecules involved. Using a powerful combination of solution NMR spectroscopy and biophysical methods the interplay between structure and motion and their impact on biological function are being determined for several enzymes. We are focusing on understanding the physical basis of allostery using the enzymes Imidazole glycerol phosphate synthase and tRNaseZ. The physico-chemical mechanism of protein motions in enzyme catalysis is being investigated in the enzymes triosephosphate isomerase and RNaseA. Our ultimate goal is to provide a more complete picture of protein function that incorporates structure as well as important time-dependent motions.





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SCL 131A