Computationally focusing the directed evolution of proteins

Directed evolution has proven to be a successful strategy for the modification of enzyme properties. To date, the preferred experimental procedure has been to apply mutations or crossovers randomly throughout the gene. With the emergence of powerful computational methods, it has become possible to develop focused combinatorial searches, guided by computer algorithms. Here, we describe several computational methods that have emerged to aid the optimization of mutant libraries, the targeting of specific residues for mutagenesis, and the design of recombination experiments. J. Cell. Biochem. Suppl. 37: 58–63, 2001. © 2002 Wiley‐Liss, Inc.

[1]  Frances H. Arnold,et al.  Computational method to reduce the search space for directed protein evolution , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Cheng Zhao,et al.  Estimation of the Mutation Rate During Error-prone Polymerase Chain Reaction , 2000, J. Comput. Biol..

[3]  Marc Ostermeier,et al.  A combinatorial approach to hybrid enzymes independent of DNA homology , 1999, Nature Biotechnology.

[4]  Melanie Mitchell,et al.  Relative Building-Block Fitness and the Building Block Hypothesis , 1992, FOGA.

[5]  R. Howard,et al.  Applications of DNA shuffling to pharmaceuticals and vaccines. , 1997, Current opinion in biotechnology.

[6]  John H. Holland,et al.  Adaptation in Natural and Artificial Systems: An Introductory Analysis with Applications to Biology, Control, and Artificial Intelligence , 1992 .

[7]  Jon E. Ness,et al.  DNA shuffling of subgenomic sequences of subtilisin , 1999, Nature Biotechnology.

[8]  Frances H. Arnold,et al.  Exploring Nonnatural Evolutionary Pathways by Saturation Mutagenesis: Rapid Improvement of Protein Function , 1999, Journal of Molecular Evolution.

[9]  Philip Pjura,et al.  Development of an in vivo method to identify mutants of phage T4 lysozyme of enhanced thermostability , 1993, Protein science : a publication of the Protein Society.

[10]  F. Arnold Combinatorial and computational challenges for biocatalyst design , 2001, Nature.

[11]  F. Arnold,et al.  Directed evolution converts subtilisin E into a functional equivalent of thermitase. , 1999, Protein engineering.

[12]  T. Yomo,et al.  Nonadditivity of mutational effects on the properties of catalase I and its application to efficient directed evolution. , 1998, Protein engineering.

[13]  F. Arnold,et al.  Directed evolution of subtilisin E in Bacillus subtilis to enhance total activity in aqueous dimethylformamide. , 1996, Protein engineering.

[14]  Gunar E. Liepins,et al.  Schema Disruption , 1991, ICGA.

[15]  C. Voigt,et al.  Rational evolutionary design: the theory of in vitro protein evolution. , 2000, Advances in protein chemistry.

[16]  S. Benkovic,et al.  Rapid generation of incremental truncation libraries for protein engineering using alpha-phosphothioate nucleotides. , 2001, Nucleic acids research.

[17]  S. L. Mayo,et al.  De novo protein design: fully automated sequence selection. , 1997, Science.

[18]  Fengzhu Sun Modeling DNA Shuffling , 1999, J. Comput. Biol..

[19]  S. Kauffman,et al.  Towards a general theory of adaptive walks on rugged landscapes. , 1987, Journal of theoretical biology.

[20]  W. Stemmer,et al.  DNA shuffling of a family of genes from diverse species accelerates directed evolution , 1998, Nature.

[21]  F. Arnold,et al.  Tuning the activity of an enzyme for unusual environments: sequential random mutagenesis of subtilisin E for catalysis in dimethylformamide. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[22]  F. Arnold,et al.  Designed evolution of enzymatic properties. , 2000, Current opinion in biotechnology.

[23]  Marc Ostermeier,et al.  Finding Cinderella's slipper—proteins that fit , 1999, Nature Biotechnology.

[24]  J W Szostak,et al.  RNA-peptide fusions for the in vitro selection of peptides and proteins. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[25]  G. Georgiou,et al.  Quantitative analysis of the effect of the mutation frequency on the affinity maturation of single chain Fv antibodies. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[26]  K D Wittrup,et al.  Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Jeffery G. Saven,et al.  STATISTICAL MECHANICS OF THE COMBINATORIAL SYNTHESIS AND ANALYSIS OF FOLDING MACROMOLECULES , 1997 .

[28]  M. Huynen,et al.  Smoothness within ruggedness: the role of neutrality in adaptation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Protein Salvage by Directed Evolution: Functional Restoration of a Defective Lysozyme Mutant , 1999, Annals of the New York Academy of Sciences.

[30]  L. Loeb,et al.  The Conserved Active Site Motif A of Escherichia coliDNA Polymerase I Is Highly Mutable* , 2001, The Journal of Biological Chemistry.

[31]  W. Stemmer Rapid evolution of a protein in vitro by DNA shuffling , 1994, Nature.