: Proc Natl Acad Sci U S A 1992 Aug 15;89(16):7811-5
An Algorithm for Protein Engineering: Simulations of Recursive Ensemble
Mutagenesis
Arkin A.P., Youvan D.C .
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
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.