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

Christopher Reynolds (1) , Christopher J Illingworth (2) , Kevin E Parkes (3) , Chris R Snell (3) , Vicent Moliner (4) , Sergio Marti (4)

1 Biological Sciences
2 Biological Sciences
3 Medivir (UK)
4 Universitat Jaume I = Jaume I University

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, we have demonstrated the feasibility of including MM polarization into these calculations using the method of induced charges. MM polarization is shown to be a short-range effect, such that 80% of the energy of MM polarization occurs within a 5 Angstrom 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.

Mots clés: Physical Sciences

Christopher Reynolds, Christopher J Illingworth, Kevin E Parkes, Chris R Snell, Vicent Moliner, et al.. The effect of MM polarization on the QM/MM transition state stabilization: application to chorismate mutase. Molecular Physics, 2008, 106 (12-13), pp.1511-1515. ⟨10.1080/00268970802077850⟩. ⟨hal-00513198⟩