James A. Wells
University of California, San Francisco
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Primary Section: 21, Biochemistry Secondary Section: 29, Biophysics and Computational Biology Membership Type:
Member
(elected 1999)
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Research Interests
My research is focused on molecular recognition in proteins and on new technologies for analysis and design of proteins and small molecules for biomedical and industrial applications. With others, I have studied key elements in catalysis and specificity in the bacterial serine protease, subtilisin, using mutational methods. Subtilisin is very adaptable enzyme and virtually every functional property has been engineered, including substrate turn-over, specificity, stability, and oxidative resistance. Our group also studies protein-protein recognition. We discovered that binding of human growth hormone (hGH) dimerizes and activates its receptor. We are also interested in the energetics of protein-protein interfaces and on designing molecular mimics for them. Although these contact interfaces cover a large surface area, we found that only a compact group of residues near the center of the interface, termed "hot spots," are crucial for binding. Such hot spots suggest it may be possible to generate small molecules that will bind at these interfaces and facilitate drug discovery.
