Quantum mechanical design of enzyme active sites.

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