López-Canut Violeta, Martí Sergio, Bertrán Juan, Moliner Vicente, Tuñón Iñaki
Departament de Química Física, Universitat de València, València, Spain.
J Phys Chem B. 2009 Jun 4;113(22):7816-24. doi: 10.1021/jp901444g.
The reaction mechanism of phosphate monoester hydrolysis in alkaline phosphatase is analyzed by means of hybrid QM/MM simulations. A recently developed semiempirical Hamiltonian, AM1/d-PhoT, which takes into account the d orbitals on the phosphorus atom, has been employed. The reaction mechanism obtained is either associative or dissociative, depending on the size of the QM subsystem. The results are rationalized on the basis of the degree of charge transfer from the reacting fragments to the two zinc ions present in the active site, which has been observed to be dependent on whether or not metal atoms and their coordination spheres are included in the QM region. The description obtained using the largest QM region agrees with the picture obtained from experimental data.
通过混合量子力学/分子力学（QM/MM）模拟分析了碱性磷酸酶中磷酸单酯水解的反应机理。采用了一种最近开发的半经验哈密顿量AM1/d-PhoT，该哈密顿量考虑了磷原子上的d轨道。根据QM子系统的大小，得到的反应机理要么是缔合的，要么是解离的。基于从反应片段到活性位点中存在的两个锌离子的电荷转移程度对结果进行了合理化解释，已观察到这种电荷转移程度取决于金属原子及其配位球是否包含在QM区域中。使用最大QM区域获得的描述与从实验数据得到的情况一致。
