title: Toward accurate barriers for enzymatic reactions: QM/MM case study on p-hydroxybenzoate hydroxylase.
abstract: The hydroxylation reaction catalyzed by p-hydroxybenzoate hydroxylase has been investigated by quantum mechanical/molecular mechanical (QM/MM) calculations at different levels of QM theory. The solvated enzyme was modeled (approximately 23,000 atoms in total, 49 QM atoms). The geometries of reactant and transition state were optimized for ten representative pathways using semiempirical (AM1) and density functional (B3LYP) methods as QM components. Single-point calculations at B3LYP/MM optimized geometries were performed with local correlation methods [LMP2, LCCSD(T0)] and augmented triple-zeta basis sets. A careful validation of the latter approach with regard to all computational parameters indicates convergence of the QM contribution to the computed barriers to within approximately 1 kcal mol(-1). Comparison with the available experimental data supports this assessment.
authors.affiliation: Institut für Theoretische Chemie, Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Mata
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Werner
authors.forename: Stephan
authors.initials: S
authors.lastname: Thiel
authors.forename: Walter
authors.initials: W
authors.lastname: Thiel
mesh_terms: D015109:4-Hydroxybenzoate-3-Monooxygenase / Q000378:metabolism*; D002384:Catalysis; D003198:Computer Simulation; D011789:Quantum Theory; D013379:Substrate Specificity
chemical_list: D015109:4-Hydroxybenzoate-3-Monooxygenase