ArticleProtein engineering, design & selection : PEDS2008
Amino acid alphabet size in protein evolution experiments: better to search a small library thoroughly or a large library sparsely?
Article in Protein engineering, design & selection : PEDS, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- PuLSE: Quality control and quantification of peptide sequences explored by phage display libraries.PloS one · 2018Article
- Directed Chemical Evolution with an Outsized Genetic Code.PloS one · 2016Article
- Trade-offs in antibody repertoires to complex antigens.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015Article
- Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently.Chemical Society reviews · 2015Review
- Microbial enzymes: tools for biotechnological processes.Biomolecules · 2014Review
- A multi-scale model for correlation in B cell VDJ usage of zebrafish.Physical biology · 2011Article
- Clustering of protein families into functional subtypes using Relative Complexity Measure with reduced amino acid alphabets.BMC bioinformatics · 2010Article
- Directed evolution drives the next generation of biocatalysts.Nature chemical biology · 2009Review
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Authors and funding
2 authors.
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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.
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