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Article

A Hybrid Potential Reaction Path and Free Energy Study of the Chorismate Mutase Reaction

Sergio Martí,^† Juan Andrés,^† Vicent Moliner,*^† Estanislao Silla,^‡ Iñaki Tuñón,*^‡ Juan Bertrán,^§ and Martin J. Field

Contribution from the Departament de Cincies Experimentals, Universitat Jaume I, Box 224, 12080 Castelln, Spain, Departament de Qumica Fsica, Universidad de Valencia, 46100 Burjasot, Valencia, Spain, Departament de Qumica, Universitat Autnoma de Barcelona, 08193 Bellaterra, Barcelona, Spain, and Laboratoire de Dynamique Molculaire, Institut de Biologie Structurale - Jean-Pierre Ebel, 38027 Grenoble Cedex 1, France

J. Am. Chem. Soc., 2001, 123 (8), pp 1709–1712

DOI: 10.1021/ja003522n

Publication Date (Web): February 3, 2001

†

Universitat Jaume I.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

‡

Universidad de Valencia.

Universitat Autónoma de Barcelona.

Institut de Biologie Structurale - Jean-Pierre Ebel.

Abstract

We present a combination of two techniquesQM/MM statistical simulation methods and QM/MM internal energy minimizationsto get a deeper insight into the reaction catalyzed by the enzyme chorismate mutase. Structures, internal energies and free energies, taken from the paths of the reaction in solution and in the enzyme have been analyzed in order to estimate the relative importance of the reorganization and preorganization effects. The results we obtain for this reaction are in good 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 that in solution by providing an environment which stabilizes the transition state.