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首页> 外文期刊>Chemical biology and drug design >Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations
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Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations

机译：小Bu碱衍生物对BuChE的分子建模：定量结构-活性关系模型，分子对接和分子动力学模拟的综合研究。

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摘要

A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R-2) of 0.883, a cross-validation correlation coefficient (Q(cv)(2) )of 0.777, and a conventional correlation coefficient of the test set (R-pred(2)) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (E-vdw) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives.
机译：基于定量结构-活性关系模型，分子对接和分子动力学方法的组合，研究了67种抑制丁酰胆碱酯酶（BuChE）的小ber碱衍生物的数据集。首先，报道了一系列小ber碱衍生物，并评估了它们对丁酰胆碱酯酶（BuChE）的抑制活性。通过2D定量结构-活性关系研究，由偏最小二乘建立的最佳模型的训练集（R-2）的常规相关系数为0.883，交叉验证相关系数（Q（cv）（2） ）为0.777，而测试集的常规相关系数（R-pred（2））为0.775。该模型还通过Y随机检验得到了证实。此外，进行了分子对接和分子动力学模拟，以更好地阐明三种典型的小ber碱衍生物（小ber碱，C2和C55）对BuChE的抑制机理。预测的结合自由能结果与实验数据一致，表明范德华能量项（E-vdw）的差异在区分三种抑制剂（小ber碱，C2和C55）的活性中起着最重要的作用。建立的定量构效关系模型提供了连接结构和活性的精细关系的详细信息，并为结构修饰提供了线索，分子模拟有助于理解这三种典型抑制剂的抑制机理。总之，这项研究的结果为新药设计和从小ber碱衍生物中发现BuChE抑制剂提供了有用的线索。

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