De novo design of biocatalysts.
The challenging field of de novo enzyme design is beginning to produce exciting results. The application of powerful computational methods to functional protein design has recently succeeded at engineering target activities. In addition, efforts in directed evolution continue to expand the transformations that can be accomplished by existing enzymes. The engineering of completely novel catalytic activity requires traversing inactive sequence space in a fitness landscape, a feat that is better suited to computational design. Optimizing activity, which can include subtle alterations in backbone conformation and protein motion, is better suited to directed evolution, which is highly effective at scaling fitness landscapes towards maxima. Improved rational design efforts coupled with directed evolution should dramatically improve the scope of de novo enzyme design.
Bolon
Daniel N
DN
Biochemistry and Molecular Biophysics Option, California Institute of Technology, mail code 147-75, Pasadena, California 91125, USA.
Voigt
Christopher A
CA
Mayo
Stephen L
SL
D017151:Antibodies, Catalytic; D002384:Catalysis; D003198:Computer Simulation; D019020:Directed Molecular Evolution; D015195:Drug Design; D004798:Enzymes / Q000138:chemical synthesis*; D018716:Molecular Mimicry
D017151:Antibodies, Catalytic; D004798:Enzymes