Details

Autor(en) / Beteiligte

• Zhang, Xiyun
• DeChancie, Jason
• Gunaydin, Hakan
• Chowdry, Arnab B
• Clemente, Fernando R
• Smith
• Handel, T. M
• Houk, K. N

Titel

Quantum Mechanical Design of Enzyme Active Sites

Ist Teil von

• Journal of organic chemistry, 2008-02, Vol.73 (3), p.889-899

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• The design of active sites has been carried out using quantum mechanical calculations to predict the rate-determining transition state of a desired reaction in presence of the optimal arrangement of catalytic functional groups (theozyme). Eleven versatile reaction targets were chosen, including hydrolysis, dehydration, isomerization, aldol, and Diels−Alder reactions. For each of the targets, the predicted mechanism and the rate-determining transition state (TS) of the uncatalyzed reaction in water is presented. For the rate-determining TS, a catalytic site was designed using naturalistic catalytic units followed by an estimation of the rate acceleration provided by a reoptimization of the catalytic site. Finally, the geometries of the sites were compared to the X-ray structures of related natural enzymes. Recent advances in computational algorithms and power, coupled with successes in computational protein design, have provided a powerful context for undertaking such an endeavor. We propose that theozymes are excellent candidates to serve as the active site models for design processes.