Title: "Exploring protein sequence space by computation guided recombination"
Speaker: Jonathan (Joff) Silberg, Division of Chemistry and Chemical Engineering, California Institute of Technology
Place: MONDAY; MAY 10, 2004: 10:30am; WTHR 201


Anecdotal evidence from laboratory evolution experiments suggests that recombination can rapidly accumulate beneficial mutations onto a single offspring and possibly find novel and beneficial combinations of amino acids that are neutral in their original, parental contexts. Little information exists, however, on the relationship between mutation level and evolution of protein function, i.e. how evolution of function scales with the number of effective mutations incorporated by recombination. We are using structure-based tools to identify polypeptide elements that can be swapped among related proteins without disrupting their three-dimensional structure. By recombining these elements in a combinatorial fashion we are creating well-defined libraries of diverse sequences (using distantly-related lactamase or cytochrome P450 homologs as parents), a large fraction of which are predicted to retain parental fold. We are analyzing the structures and activities of proteins in these chimeric libraries to determine the quality of structure-based tools, and investigating whether these proteins can display interesting behaviors, including ones not known in nature.

(This is a candidate for the Bioinformatics COALESCE hires in the School of Science. To meet with the candidate, please contact RW Doerge at doerge@purdue.edu)

See http://www.stat.purdue.edu/~doerge/BIOINFORM.D/SPRING04/sem.html for a full scheule of BIOINFORMATICS SEMINARS.