Review
Computational Enzyme Design
Dr. Gert Kiss,
Dr. Nihan Çelebi-Ölçüm,
Dr. Rocco Moretti,
Prof. Dr. David Baker,
Prof. Dr. Dr. K. N. Houk,
Dr. Gert Kiss
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles CA, 90095 (USA)
Current address: Department of Chemistry, Stanford University, Stanford, CA 94305 (USA)
Search for more papers by this authorDr. Nihan Çelebi-Ölçüm
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles CA, 90095 (USA)
Current address: Yeditepe University, Department of Chemical Engineering, Istanbul (Turkey)
Search for more papers by this authorDr. Rocco Moretti
Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195 (USA)
Search for more papers by this authorProf. Dr. David Baker
Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Dr. K. N. Houk
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles CA, 90095 (USA)
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles CA, 90095 (USA)Search for more papers by this authorDr. Gert Kiss,
Dr. Nihan Çelebi-Ölçüm,
Dr. Rocco Moretti,
Prof. Dr. David Baker,
Prof. Dr. Dr. K. N. Houk,
Dr. Gert Kiss
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles CA, 90095 (USA)
Current address: Department of Chemistry, Stanford University, Stanford, CA 94305 (USA)
Search for more papers by this authorDr. Nihan Çelebi-Ölçüm
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles CA, 90095 (USA)
Current address: Yeditepe University, Department of Chemical Engineering, Istanbul (Turkey)
Search for more papers by this authorDr. Rocco Moretti
Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195 (USA)
Search for more papers by this authorProf. Dr. David Baker
Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Dr. K. N. Houk
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles CA, 90095 (USA)
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles CA, 90095 (USA)Search for more papers by this authorGraphical Abstract
The “inside-out” approach to computer-based enzyme design unites the newest developments in the areas of computational chemistry and biology. This has enabled the design of proteins that catalyze reactions not accelerated in nature. The achievements and limitations of the current technology are highlighted and compared to other methods.
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.
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