Computing kinetic isotope effects for chorismate mutase with high accuracy. A new DFT/MM strategy

J Phys Chem B. 2005 Mar 10;109(9):3707-10. doi: 10.1021/jp044387u.


A novel procedure has been applied to compute experimentally unobserved intrinsic kinetic isotope effects upon the rearrangement of chorismate to prephenate catalyzed by B. subtilis chorismate mutase. In this modified QM/MM approach, the "low-level" QM description of the quantum region is corrected during the optimization procedure by means of a "high-level" calculation in vacuo, keeping the QM-MM interaction contribution at a quantum "low-level". This allows computation of energies, gradients, and Hessians including the polarization of the QM subsystem and its interaction with the MM environment, both terms calculated using the low-level method at a reasonable computational cost. New information on an important enzymatic transformation is provided with greater reliability than has previously been possible. The predicted kinetic isotope effects on Vmax/Km are 1.33 and 0.86 (at 30 degrees C) for 5-3H and 9-3H2 substitutions, respectively, and 1.011 and 1.055 (at 22 degrees C) for 1-13C and 7-18O substitutions, respectively.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chorismate Mutase / chemistry*
  • Isotopes / chemistry*
  • Kinetics
  • Quantum Theory


  • Isotopes
  • Chorismate Mutase