Library analysis of SCHEMA‐guided protein recombination

• DOI: 10.1110/ps.0306603
• Publication Date: 2004-02-24T22:18:09Z
• Authors: Michelle M. Meyer; Jonathan J. Silberg; Christopher A. Voigt; Jeffrey B. Endelman; Stephen L. Mayo; Zhen‐Gang Wang; Frances H. Arnold
• Keywords: Chimera (genetics); Schema (genetic algorithms)

Abstract The computational algorithm SCHEMA was developed to estimate the disruption caused when amino acid residues that interact in three‐dimensional structure of a protein are inherited from different parents upon recombination. To evaluate how well predicts disruption, we have shuffled distantly‐related β‐lactamases PSE‐4 and TEM‐1 at 13 sites create library 2 14 (16,384) chimeras examined which ones retain lactamase function. Sequencing genes ampicillin‐selected clones revealed percentage functional decreased exponentially with increasing calculated ( E = number residue–residue contacts broken recombination). We also found low higher probability maintaining function than same effective level mutation but chosen random library. Thus, simple distance metric used by identify interactions compute allows one predict chimera sequences most likely their This approach can be crossover for recombination highly mosaic, folded chimeras.