Computational design of biological catalysts.

The purpose of this tutorial review is to illustrate the way to design new and powerful catalysts. The first possibility to get a biological catalyst for a given chemical process is to use existing enzymes that catalyze related reactions. The second possibility is the use of immune systems that recognize stable molecules resembling the transition structure of the target reaction. We finally show how computational techniques are able to provide an enormous quantity of information, providing clues to guide the development of new biological catalysts.

[1]  Eric A. Althoff,et al.  Kemp elimination catalysts by computational enzyme design , 2008, Nature.

[2]  Eric A. Althoff,et al.  De Novo Computational Design of Retro-Aldol Enzymes , 2008, Science.

[3]  J. Bertrán,et al.  Predicting an improvement of secondary catalytic activity of promiscuous isochorismate pyruvate lyase by computational design. , 2008, Journal of the American Chemical Society.

[4]  David Baker,et al.  Protein-protein docking with backbone flexibility. , 2007, Journal of molecular biology.

[5]  Frances H Arnold,et al.  Engineering by homologous recombination: exploring sequence and function within a conserved fold. , 2007, Current opinion in structural biology.

[6]  Stephen L Mayo,et al.  Exhaustive mutagenesis of six secondary active-site residues in Escherichia coli chorismate mutase shows the importance of hydrophobic side chains and a helix N-capping position for stability and catalysis. , 2007, Biochemistry.

[7]  Patricia C Babbitt,et al.  Stability for function trade-offs in the enolase superfamily "catalytic module". , 2007, Biochemistry.

[8]  Donald Hilvert,et al.  Minimalist active-site redesign: teaching old enzymes new tricks. , 2007, Angewandte Chemie.

[9]  Benjamin D Allen,et al.  Combinatorial methods for small-molecule placement in computational enzyme design , 2006, Proceedings of the National Academy of Sciences.

[10]  Giuseppe Manco,et al.  The latent promiscuity of newly identified microbial lactonases is linked to a recently diverged phosphotriesterase. , 2006, Biochemistry.

[11]  Dan S. Tawfik,et al.  Enzyme promiscuity: evolutionary and mechanistic aspects. , 2006, Current opinion in chemical biology.

[12]  Timothy D. Fenn,et al.  Structural and functional comparisons of nucleotide pyrophosphatase/phosphodiesterase and alkaline phosphatase: implications for mechanism and evolution. , 2006, Biochemistry.

[13]  Alejandro J. Vila,et al.  Metallo-β-lactamases: Novel Weaponry for Antibiotic Resistance in Bacteria , 2006 .

[14]  A. Warshel,et al.  Electrostatic basis for enzyme catalysis. , 2006, Chemical reviews.

[15]  Thomas E. Ferrin,et al.  Designed divergent evolution of enzyme function , 2006, Nature.

[16]  D. Baker,et al.  Improvement in protein functional site prediction by distinguishing structural and functional constraints on protein family evolution using computational design , 2005, Nucleic acids research.

[17]  R. Kazlauskas,et al.  Improving enzyme properties: when are closer mutations better? , 2005, Trends in biotechnology.

[18]  Stephen L Mayo,et al.  Computationally designed variants of Escherichia coli chorismate mutase show altered catalytic activity. , 2005, Protein engineering, design & selection : PEDS.

[19]  Sergio Martí,et al.  Theoretical insights in enzyme catalysis. , 2004, Chemical Society reviews.

[20]  D. Hilvert,et al.  Promiscuity in Antibody Catalysis: Esterolytic Activity of the Decarboxylase 21D8 , 2003 .

[21]  S. Copley.  Enzymes with extra talents: moonlighting functions and catalytic promiscuity. , 2003, Current opinion in chemical biology.

[22]  Beth M Beadle,et al.  Structural bases of stability-function tradeoffs in enzymes. , 2002, Journal of molecular biology.

[23]  Brian K Shoichet,et al.  Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs. , 2002, Journal of molecular biology.

[24]  S. L. Mayo,et al.  Enzyme-like proteins by computational design , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Wolfenden,et al.  The depth of chemical time and the power of enzymes as catalysts. , 2001, Accounts of chemical research.

[26]  M. Field,et al.  A hybrid potential reaction path and free energy study of the chorismate mutase reaction. , 2001, Journal of the American Chemical Society.

[27]  Christopher A. Voigt,et al.  Trading accuracy for speed: A quantitative comparison of search algorithms in protein sequence design. , 2000, Journal of molecular biology.

[28]  D. Herschlag,et al.  Catalytic promiscuity and the evolution of new enzymatic activities. , 1999, Chemistry & biology.

[29]  F. Arnold.  Design by Directed Evolution , 1998 .

[30]  W. Richards,et al.  Insights into Chorismate Mutase Catalysis from a Combined QM/MM Simulation of the Enzyme Reaction , 1995 .

[31]  A. Warshel,et al.  Energetics of enzyme catalysis. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Levitt,et al.  Theoretical studies of enzymic reactions: dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme. , 1976, Journal of molecular biology.

[33]  J. Bertran,et al.  Computer-aided rational design of catalytic antibodies: The 1F7 case. , 2007, Angewandte Chemie.

[34]  M. Sutcliffe,et al.  Insights into drug metabolism from modelling studies of cytochrome P450-drug interactions. , 2006, Current topics in medicinal chemistry.

[35]  Dan S. Tawfik,et al.  The 'evolvability' of promiscuous protein functions , 2005, Nature Genetics.

[36]  D. Hilvert.  Critical analysis of antibody catalysis. , 2000, Annual review of biochemistry.