Enzyme millisecond conformational dynamics do not catalyze the chemical step

Andrei V. Pisliakov, Jie Cao, Shina C.L. Kamerlin, Arieh Warshel (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    175 Citations (Scopus)

    Abstract

    The idea that enzymes catalyze reactions by dynamical coupling between the conformational motions and the chemical coordinates has recently attracted major experimental and theoretical interest. However, experimental studies have not directly established that the conformational motions transfer energy to the chemical coordinate, and simulating enzyme catalysis on the relevant timescales has been impractical. Here, we introduce a renormalization approach that transforms the energetics and dynamics of the enzyme to an equivalent low-dimensional system, and allows us to simulate the dynamical coupling on a ms timescale. The simulations establish, by means of several independent approaches, that the conformational dynamics is not remembered during the chemical step and does not contribute significantly to catalysis. Nevertheless, the precise nature of this coupling is a question of great importance.
    Original languageEnglish
    Pages (from-to)17359-17364
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume106
    Issue number41
    DOIs
    Publication statusPublished - 13 Oct 2009

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