Toward accurate barriers for enzymatic reactions:: QM/MM case study on p-hydroxybenzoate hydroxylase
Toward accurate barriers for enzymatic reactions:: QM/MM case study on p-hydroxybenzoate hydroxylase
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DOI：
10.1063/1.2823055
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发表时间：
2008-01-14
影响因子：
4.4
通讯作者：
Thiel, Walter
中科院分区：
文献类型：
--
作者：
Mata, Ricardo A.;Werner, Hans-Joachim;Thiel, Walter
采用量子力学/分子力学（QM/MM）方法，在不同水平上研究了对羟基苯甲酸羟化酶催化的羟化反应。溶剂化的酶被建模（类似于总共23000个原子，49个QM原子）。采用半经验（AM 1）和密度泛函（B3 LYP）方法对10种典型反应途径的反应物和过渡态的几何构型进行了优化。在B3 LYP/MM优化的几何构型下，使用局部相关方法[LMP 2，LCCSD（T0）]和增强的三重zeta基组进行单点计算。仔细验证后一种方法的所有计算参数表明收敛的QM贡献的计算障碍内类似1千卡摩尔（-1）。与现有实验数据的比较支持这一评估。(c)2008年美国物理研究所。
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 (similar to 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 similar to 1 kcal mol(-1). Comparison with the available experimental data supports this assessment. (c) 2008 American Institute of Physics.