Quantum Mechanical Design and Evaluation of Active Sites of Novel Enzymes

Abstract

Active sites of enzymes have been designed from quantum mechanical calculations of transition states of reactions catalyzed by the functional side chain and backbone groups of proteins. Theoretical active sites, “theozymes,” have been developed for a variety of aldol, Diels-Alder, and eliminations reactions. Predictions of the acceleration relative to uncatalyzed have been made from a variety of quantum mechanical methods. Predictions of protein sequences and structures containing this active site were made by David Baker (U. Washington, Seattle). These designs have been evaluated quantum mechanically to determine which are promising for experimental exploration.