title: Computational enzyme design.
abstract: Recent developments in computational chemistry and biology have come together in the "inside-out" approach to enzyme engineering. Proteins have been designed to catalyze reactions not previously accelerated in nature. Some of these proteins fold and act as catalysts, but the success rate is still low. The achievements and limitations of the current technology are highlighted and contrasted to other protein engineering techniques. On its own, computational "inside-out" design can lead to the production of catalytically active and selective proteins, but their kinetic performances fall short of natural enzymes. When combined with directed evolution, molecular dynamics simulations, and crowd-sourced structure-prediction approaches, however, computational designs can be significantly improved in terms of binding, turnover, and thermal stability.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles, CA 90095, USA.
authors.forename: Gert
authors.initials: G
authors.lastname: Kiss
authors.forename: Nihan
authors.initials: N
authors.lastname: Çelebi-Ölçüm
authors.forename: Rocco
authors.initials: R
authors.lastname: Moretti
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
mesh_terms: D017151:Antibodies, Catalytic / Q000737:chemistry; D019295:Computational Biology; D004798:Enzymes / Q000737:chemistry*; D008958:Models, Molecular; D015202:Protein Engineering / Q000379:methods*
chemical_list: D017151:Antibodies, Catalytic; D004798:Enzymes