期刊
JOURNAL OF THEORETICAL BIOLOGY
卷 259, 期 3, 页码 641-645出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2009.04.008
关键词
Protein engineering; Direct evolution; Random mutagenesis; Statistics; Probability
资金
- Yale School of Medicine
Randomized libraries are increasingly popular in protein engineering and other biomedical research fields. Statistics of the libraries are useful to guide and evaluate randomized library construction. Previous works only give the mean of the number of unique sequences in the library, and they can only handle equal molar ratio of the four nucleotides at a small number of mutation sites. We derive formulas to calculate the mean and variance of the number of unique sequences in libraries generated by cassette mutagenes is with mixtures of arbitrary nucleotide ratios. Computer program was developed which utilizes arbitrary numerical precision software package to calculate the statistics of large libraries. The statistics of library with mutations in more than 20 amino acid scan be calculated easily. Results show that the nucleotide ratios have significant effects on these statistics. The more skewed the ratio, the larger the library size is needed to obtain the same expected number of unique sequences. The program is freely available at http://graphics.med.yale.edu/cgi-bin/lib_comp.pl. (C) 2009 Elsevier Ltd. All rights reserved.
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