I. Protein Design by Computation
II. Designing Protein Libraries and an Example of Making a Better Fluorescent Protein
Part I: Protein Design by Computation
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In this lecture, I discuss the challenges of designing new proteins that fold into a particular structure or perform a particular function. One method is to computationally design a protein based solely upon our knowledge of amino acids and protein folding, a hard task but one which has had recent successes.
Another approach is to screen combinatorial libraries of proteins for a desired function. In particular, I will discuss how structure-based computational methods can allow for high mutation rate (to explore a diversity of function) while maintaining stably folded structures (a necessity to preserve stability and function). In the last part of my talk, I discuss how we have used protein libraries to design a new blue fluorescent protein.
Stephen L. Mayo is currently Vice Provost (research) and Bren Professor of Biology and Chemistry at Caltech, where he has been a faculty since 1992. Dr. Mayor earned his B.S. in Chemistry at the Pennsylvania State University, and received a Ph.D. in Chemistry from Caltech in 1987. He did postdoctoral work as a Miller Fellow in the Chemistry Department at UC Berkeley and a second postdoctoral fellowship at the Biochemistry Dept. at Stanford University.
Dr. Mayo's has been a scientific leader in protein design, incorporating interface theory, computation, and experimental approaches. Dr. Mayo honors include being named a Howard Hughes Medical Institute Investigator, a Rita Allen Foundation Scholar, a David and Lucile Packard Foundation Fellow, and a Searle Scholar. He was awarded the Johnson Foundation Prize for Innovative Research in Structural Biology and is a member of the National Academy of Sciences.
Treynor, T.P., Vizcarra, C.L, Nedelcu, D., and Mayo, S.L. (2007) Computationally designed libraries of fluorescent proteins evaluated by preservation and diversity of function. Proc. Natl. Acad. Sci. U.S.A. 104:48-53.
Mena, M.A., Treynor, T.P., Mayo, S.L., and Daugherty, P.S. (2006) Blue fluorescent proteins with enhanced brightness and photostability from a structurally targeted library. Nat. Biotechnol. 24:1569-1571.
Alvizo, O., Allen, B.D., and Mayo, S.L. (2007) Computational protein design promises to revolutionize protein engineering. Biotechniques. 42:31
Bolon, D.N., Voigt, C.A., and Mayo, S.L. (2002) De novo design of biocatalysts. Curr. Opin. Chem. Biol. 6:125-129.