The role of reorganization energy in rational enzyme design.
Computational design is becoming an integral component in developing novel enzymatic activities. Catalytic efficiencies of man-made enzymes however are far behind their natural counterparts. The discrepancy between laboratory and naturally evolved enzymes suggests that a major catalytic factor is still missing in the computational process. Reorganization energy, which is the origin of catalytic power of natural enzymes, has not been exploited yet for design. As exemplified in case of KE07 Kemp eliminase, this quantity is optimized by directed evolution. Mutations beneficial for evolution, but without direct impact on catalysis can be identified based on contributions to reorganization energy. We propose to incorporate the reorganization energy in scaffold selection to provide highly evolvable initial designs.
MTA-DE Momentum Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, University of Debrecen, Hungary. Electronic address: fmoni@med.unideb.hu.
Monika
M
Fuxreiter
Department of Engineering, University of Cambridge, United Kingdom.
Letif
L
Mones
D055162:Biocatalysis; D017076:Computer-Aided Design; D019020:Directed Molecular Evolution; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D013816:Thermodynamics
D004798:Enzymes