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

Abstract

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