氨基酸残基配合物碱基对的<i>ABEEMσπ</i>极化力场的<i>研究</i>,Journal of Chemical Theory and Computation

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氨基酸残基配合物碱基对的ABEEMσπ极化力场的研究
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2017-04-18 00:00:00 , DOI: 10.1021/acs.jctc.6b01206
Cui Liu ₁ , Yue Li ₁ , Bing-Yu Han ₁ , Li-Dong Gong ₁ , Li-Nan Lu ₁ , Zhong-Zhi Yang ₁ , Dong-Xia Zhao ₁

Affiliation

氧化碱基造成的DNA损伤可导致生物衰老和癌症。幸运的是，修复酶能够修复氧化的碱基。关键步骤是准确识别主要依赖于复杂氢键相互作用的氧化碱基。我们已经校准了ABEEMσπ极化力场（ABEEMσπPFF）的电荷参数和扭转参数，以准确描述分子间和分子内的相互作用。以实验和量子化学方法为基准，计算了碱基对氨基酸残基系统，DNA和DNA-蛋白质相互作用系统的一系列特性，并将其与其他力场的特性进行了比较。我们已经在测试，校准和分析中完成了大量任务。阿贝姆σπPFF不仅明确给出了孤对电子的位置和部分电荷，而且引入了函数k _HB以适合氢键相互作用区域中的特殊静电相互作用。因此，它可以精确地模拟极化作用和氢键相互作用的电荷转移，特别是对于带电系统和含硫系统，例如诱导的氨基酸和碱基对之间的结合能（24-28 kcal / mol）通过电荷转移。ABEEMσπ的RMSDPFF为1.18 kcal / mol，而琥珀色OL15的RMSD为8.21 kcal / mol。当通过固定电荷力场模拟时，氨基酸残基的相对位置发生了显着变化，并且氢键断裂。此外，由于重新设置了合理的扭转参数，通过ABEEMσπPFF优化的几何结构与M06-2X / 6-311 ++ G **方法的几何结构非常一致，但是通过固定力场进行的模拟具有很大的优势。甲基的旋转和碱基对平面的扭曲。在用四个测试DNA和一个DNA-蛋白质系统进行广泛的MD模拟后，我们得出的结论是，与实验结构相比，ABEEMσπPFF显示出更好的一致性，这说明了我们模型的可靠性和参数的可传递性。

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Development of the ABEEMσπ Polarization Force Field for Base Pairs with Amino Acid Residue Complexes

DNA damage caused by oxidized bases can lead to aging and cancer in living beings. Luckily, a repair enzyme is able to repair the oxidized bases. The key step is to accurately recognize the oxidized bases, which mainly rely on complex hydrogen bond interactions. We have calibrated the charge parameters and torsional parameters of the ABEEMσπ polarization force field (ABEEMσπ PFF) to accurately describe the intermolecular and intramolecular interactions. Taking the experiment and quantum chemical method as the benchmark, a series of properties of base pair-amino acid residue systems, DNA and DNA–protein interaction systems were calculated and compared with those of other force fields. We have done a tremendous amount of tasks in testing, calibrations, and analyses. The ABEEMσπ PFF not only explicitly gives the position and the partial charge of lone-pair electrons but also introduces a function k_HB to fit special electrostatic interactions in hydrogen bond interaction regions. Therefore, it can accurately simulate the polarization effect and charge transfer of hydrogen bond interactions, especially for charged systems and sulfur-containing systems, such as the binding energy between amino acid and base pairs (24–28 kcal/mol), which is induced by charge transfer. The RMSD of ABEEMσπ PFF is 1.18 kcal/mol, whereas the RMSD of Amber OL15 is 8.21 kcal/mol. The relative positions of the amino acid residue have significantly changed, and the hydrogen bonds were broken when simulated by fixed charge force fields. In addition, owing to refitting the reasonable torsional parameters, the geometric structures optimized by ABEEMσπ PFF were well consistent with those of the M06-2X/6-311++G** method, but the simulations by fixed force fields have a large rotation of methyl and distortion of the plane of the base pair. After extensive MD simulation with four test DNAs and a DNA–protein system, we conclude that ABEEMσπ PFF shows better agreement when compared to experimental structures, which illustrates the reliability of our model and the transferability of the parameters.

更新日期：2017-04-18

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