Open AccessAn algorithm for protein engineering: simulations of recursive ensemble mutagenesis.
Author(s) -
Adam P. Arkin,
Douglas C. Youvan
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.16.7811
Subject(s) - mutagenesis , sequence space , algorithm , protein engineering , sequence (biology) , computer science , mutation , computational biology , selection (genetic algorithm) , population , genetics , biology , mathematics , artificial intelligence , gene , biochemistry , demography , sociology , pure mathematics , banach space , enzyme
An algorithm for protein engineering, termed recursive ensemble mutagenesis, has been developed to produce diverse populations of phenotypically related mutants whose members differ in amino acid sequence. This method uses a feedback mechanism to control successive rounds of combinatorial cassette mutagenesis. Starting from partially randomized "wild-type" DNA sequences, a highly parallel search of sequence space for peptides fitting an experimenter's criteria is performed. Each iteration uses information gained from the previous rounds to search the space more efficiently. Simulations of the technique indicate that, under a variety of conditions, the algorithm can rapidly produce a diverse population of proteins fitting specific criteria. In the experimental analog, genetic selection or screening applied during recursive ensemble mutagenesis should force the evolution of an ensemble of mutants to a targeted cluster of related phenotypes.