title: Computing kinetic isotope effects for chorismate mutase with high accuracy. A new DFT/MM strategy.
abstract: 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.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martí
authors.forename: Vicent
authors.initials: V
authors.lastname: Moliner
authors.forename: Iñaki
authors.initials: I
authors.lastname: Tuñón
authors.forename: Ian H
authors.initials: IH
authors.lastname: Williams
mesh_terms: D002826:Chorismate Mutase / Q000737:chemistry*; D007554:Isotopes / Q000737:chemistry*; D007700:Kinetics; D011789:Quantum Theory
chemical_list: D007554:Isotopes; D002826:Chorismate Mutase