QM and QM-FE simulations on reactions of relevance to enzyme catalysis: trypsin, catechol O-methyltransferase, beta-lactamase and pseudouridine synthase

The application of the quantum mechanics-free energy hybrid technique (QM-F E) to calculate the free energy changes in two enzymatic reaction systems, trypsin and catechol O-methyltransferase (COMT) is reported. The results ra tionalize the observed rate enhancements by comparing the reactions in enzy me and in aqueous solution. Quantum mechanical studies of the model systems of beta-lactamase and pseudouridine synthase systems are also presented. F or beta-lactamase, the effect of solvation on hydrolysis and methanolysis o f beta-lactams has been investigated. For pseudouridine synthase, the first steps of two different proposed mechanisms have been modeled.