A hybrid potential reaction path and free energy study of the chorismate mutase reaction

We present a combination of two techniques-QM/MM statistical simulation met hods and QM/MM internal energy minimizations-to get a deeper insight into t he reaction catalyzed by the enzyme chorismate mutase. Structures, internal energies and free energies, taken from the paths of the reaction in soluti on and in the enzyme have been analyzed in order to estimate the relative i mportance of the reorganization and preorganization effects. The results we obtain for this reaction are in good a,agreement with experiment and show that chorismate mutase achieves its catalytic efficiency in two ways; first , it preferentially binds the active conformer of the substrate and, second , it reduces the free energy of activation for the reaction relative to tha t in solution by providing an environment which stabilizes the transition s tate.