Theoretical QM/MM studies of enzymatic pericyclic reactions

S. Martí, J. Andrés, V. Moliner, E. Silla, I. Tuñón, J. Bertrán

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    7 Citations (Scopus)


    The chorismate to prephenate enzyme catalyzed reaction has been used in this review as the conduit to show different theoretical approaches that have been used over the years in our laboratory to explain its molecular mechanism. This pericyclic reaction has the advantage that other protein scaffolds such as catalytic antibodies or some promiscuous enzymes present certain chorismate mutase activity. The obtained results on all these protein environments, by comparison with the uncatalyzed reaction in solution, have been used to propose, as a general conclusion, that the origin of enzyme catalysis is in the relative electrostatic stabilization of the transition state with respect to the Michaelis complex. This feature implies that reactants of catalyzed reaction were closer to the transition state than those of the non-catalyzed reaction. From this hypothesis, and considering the features of the wild type chorismate mutases as the optimal catalyst for the reaction, some mutations on both kinds of alternative proteins have been proposed which would presumably enhance the rate constant of the chemical step. The studies presented in this paper demonstrate that the improvements and developments of the methods and techniques of theoretical and computational chemistry are now mature enough to model physic-chemical properties of biological systems with good accuracy. The combination of a potent computational protocol with molecular engineering techniques can be a promising methodology to develop novel enzymes with new or more efficient catalytic functions. © 2010 International Association of Scientists in the Interdisciplinary Areas and Springer Berlin Heidelberg.
    Original languageEnglish
    Pages (from-to)115-131
    JournalInterdisciplinary Sciences: Computational Life Sciences
    Issue number1
    Publication statusPublished - 1 Mar 2010


    • catalytic antibodies
    • chorismate mutase
    • enzyme peryciclic reactions
    • enzyme reaction mechanisms
    • free energy profiles
    • Potential of Mean Force
    • QM/MM


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