The effect of MM polarization on the QM/MM transition state stabilization: Application to chorismate mutase

C. J.R. Illingworth, K. E. Parkes, C. R. Snell, S. Marti, V. Moliner, C. A. Reynolds

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Hybrid quantum mechanics/molecular mechanics (QM/MM) calculations provide a mechanism for studying enzyme catalysed reactions at the molecular level. Here, through applications on the chorismate to prephenate rearrangement within the enzyme chorismate mutase, the feasibility of including MM polarization into these calculations has been demonstrated using the method of induced charges. MM polarization is shown to be a short-range effect, such that more than 75% of the energy of MM polarization occurs within a 5 Å residue-based cut-off of the substrate. MM polarization was shown to have a greater magnitude within the enzyme catalysed reaction than in the aqueous reaction, indicating that MM polarization may in principle have a significant effect on enzyme rate enhancement and mechanism. In both the enzyme and the aqueous case, the percentage contribution of MM polarization to the total stabilization energy was towards the upper end of the expected value. For the specific structures studied here, MM polarization lowered the energy barrier for the aqueous reaction, but the calculated contribution of MM polarization to both the reactant and transition structure stability were similar.

Original languageEnglish
Pages (from-to)1511-1515
Number of pages5
JournalMolecular Physics
Volume106
Issue number12-13
DOIs
Publication statusPublished - 1 Jun 2008
Externally publishedYes

Keywords

  • Chorismate mutase
  • Induced charge
  • Polarization
  • QM/MM
  • Transition state stabilization

ASJC Scopus subject areas

  • Biophysics
  • Molecular Biology
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

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