title: Computer aided enzyme design and catalytic concepts.
abstract: Gaining a deeper understanding of enzyme catalysis is of great practical and fundamental importance. Over the years it has become clear that despite advances made in experimental mutational studies, a quantitative understanding of enzyme catalysis will not be possible without the use of computer modeling approaches. While we believe that electrostatic preorganization is by far the most important catalytic factor, convincing the wider scientific community of this may require the demonstration of effective rational enzyme design. Here we make the point that the main current advances in enzyme design are basically advances in directed evolution and that computer aided enzyme design must involve approaches that can reproduce catalysis in well-defined test cases. Such an approach is provided by the empirical valence bond method.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Frushicheva
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Matthew J L
authors.initials: MJ
authors.lastname: Mills
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schopf
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Singh
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Ram B
authors.initials: RB
authors.lastname: Prasad
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: Warshel@usc.edu.
authors.forename: Arieh
authors.initials: A
authors.lastname: Warshel
mesh_terms: D055162:Biocatalysis; D020134:Catalytic Domain; D017076:Computer-Aided Design; D004798:Enzymes / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D015202:Protein Engineering / Q000379:methods*
chemical_list: D004798:Enzymes