Improvement of the self-consistent-charge density-functional-tight-binding theory by a modified Mulliken charge
Improvement of the self-consistent-charge density-functional-tight-binding theory by a modified Mulliken charge
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改进的马利肯电荷对自洽电荷密度泛函紧束缚理论的改进
DOI：
10.1007/s00214-017-2156-1
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发表时间：
2017
影响因子：
1.7
通讯作者：
Yao Jianzhuang
中科院分区：
文献类型：
--
作者：
Wang;Xia;Yao Jianzhuang
尽管人们为提高自洽电荷密度功能紧结合（SCC-DFTB）的准确性进行了广泛的努力，但SCC-DFTB在生物系统（例如酶）上的应用仍然有限。我们的基准计算表明，原始的 SCC-DFTB/MM 无法正确描述人羧酸酯酶 1 (CES1) 催化的 d-苏型哌甲酯 (dMD) 水解。与从头开始的 QM/MM 结果相反，SCC-DFTB/MM 低估了活化自由能势垒，并使酰化过程成为单步反应，无需四面体中间体。似乎 SCC-DFTB/MM 错误地估计了氧阴离子空穴中底物氧原子的负 QM Mulliken 电荷。为了提高SCC-DFTB能量以及QM（SCC-DFTB）和MM原子之间的静电相互作用，我们采用了QM Mulliken电荷的优化策略，其中训练经验参数以沿着反应坐标将SCC-DFTB Mulliken电荷拟合到高级DFT方法。这里，优化的基于Mulliken电荷的SCC-DFTB方法被表示为SCC-DFTBMR。最后，进行基准和自由能计算，以证明 SCC-DFTBMR 对 CES1 催化反应的适用性。
Although extensive efforts had been carried out to improve the accuracy of the self-consistent-charge density-functional-tight-binding (SCC-DFTB), the application of SCC-DFTB on biological systems (e.g., enzymes) is still limited. Our benchmark calculations show that the original SCC-DFTB/MM is not able to properly descript the human carboxylesterase 1 (CES1) catalyzed hydrolysis ofd-threo-methylphenidate (dMD). In contrast to the ab initio QM/MM results, SCC-DFTB/MM underestimates the activation free energy barrier and renders the acylation process as a single-step reaction without a tetrahedral intermediate. It seems like that SCC-DFTB/MM misestimates the developing negative QM Mulliken charge of the substrate oxygen atom in the oxyanion hole. To improve the SCC-DFTB energy and the electrostatic interaction between QM (SCC-DFTB) and MM atoms, we adopt an optimization strategy for QM Mulliken charge, in which an empirical parameter is trained to fit the SCC-DFTB Mulliken charge to high-level DFT method along the reaction coordinate. Herein, the optimized Mulliken charge-based SCC-DFTB method is denoted as SCC-DFTBMR. Finally, benchmark and free energy calculations were performed to prove the applicability of SCC-DFTBMR to CES1-catalyzed reaction.