title: Amino acid alphabet size in protein evolution experiments: better to search a small library thoroughly or a large library sparsely?
abstract: We compare the results obtained from searching a smaller library thoroughly versus searching a more diverse, larger library sparsely. We study protein evolution with reduced amino acid alphabets, by simulating directed evolution experiments at three different alphabet sizes: 20, 5 and 2. We employ a physical model for evolution, the generalized NK model, that has proved successful in modeling protein evolution, antibody evolution and T-cell selection. We find that antibodies with higher affinity are found by searching a library with a larger alphabet sparsely than by searching a smaller library thoroughly, even with well-designed reduced libraries. We also find ranked amino acid usage frequencies in agreement with observations of the CDR-H3 variable region of human antibodies.
authors: Department of Bioengineering, Rice University, Houston, TX 77005-1892, USA.
authors: Enrique
authors: E
authors: Muñoz
authors: Michael W
authors: MW
authors: Deem
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D003198:Computer Simulation; D019277:Entropy; D019143:Evolution, Molecular; D015723:Gene Library; D015233:Models, Statistical; D009010:Monte Carlo Method; D019151:Peptide Library; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D000596:Amino Acids; D019151:Peptide Library; D011506:Proteins