Algorithms for Joint Optimization of Stability and Diversity in Planning Combinatorial Libraries of Chimeric Proteins

Abstract. In engineering protein variants by constructing and screening combinatorial libraries of chimeric proteins, two complementary and competing goals are desired: the new proteins must be similar enough to the evolutionarily-selected wild-type proteins to be stably folded, and they must be different enough to display functional variation. We present here the first method, Staversity, to simultaneously optimize stability and diversity in selecting sets of breakpoint locations for site-directed recombination. Our goal is to uncover all "undominated" breakpoint sets, for which no other breakpoint set is better in both factors. Our first algorithm finds the undominated sets serving as the vertices of the lower envelope of the two-dimensional (stability and diversity) convex hull containing all possible breakpoint sets. Our second algorithm identifies additional breakpoint sets in the concavities that are either undominated or dominated only by undiscovered breakpoint sets w...

• Type: Conference
• Year: 2008
• Where: RECOMB
• Authors: Wei Zheng, Alan M. Friedman, Chris Bailey-Kellogg
• Keywords: Breakpoint Sets, Computational Biology, Engineering Protein Variants, Possible Breakpoint Sets, RECOMB 2008