黄酮类衍生物抗癌活性的分子对接、分子动力学模拟和定量构效关系研究
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- 英文论文题名：Combined molecular docking,molecular dynamics simulation and QSAR study of flavonoid derivatives as anticancer drugs
- 论文作者：黄相中 ; 侯书群 ; 夏福婷 ; 李艳红 ; 王韦 ; 田凯
- 英文论文作者：Xiang-Zhong Huang ; Shu-Qun Hou ; Futing Xia ; Yanhong Li ; Wei Wang ; Kai Tian ; School of Ethnic Medicine ; Yunnan Minzu University ; School of Chemistry and Environment ; Yunnan Minzu University
- 年：2016
- 作者机构：云南民族大学民族医药学院;云南民族大学化学与环境学院;
- 论文关键词：黄酮类衍生物 ; 核因子-κ蛋白激酶 ; 3D-QSAR ; 分子对接 ; 分子动力学模拟
- 英文论文关键词：Flavonoid derivatives ; Nuclear factor-kappa protein kinase ; 3D-QSAR ; Molecular docking ; Molecular dynamics simulation
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十五分会：化学信息学与化学计量学
- 语种：中文
- 分类号：TQ460.1
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十五分会 ; 化学信息学与化学计量学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：205k
- 原文格式：D
- 会议级别：全国
摘要
研究具有抗癌活性的黄酮类衍生物的定量构效关系(QSAR)、对接分析、作用机理及分子动力学的模拟。首先,利用传统的多元线性回归、基于SMILES编码的新型方法、3D-QSAR中的比较分子力场分析(CoMFA)与比较分子相似性指数分析(CoMSIA)对作为核因子-κ蛋白激酶抑制剂的一系列黄酮类衍生物的结构与活性关系进行了研究,得到了多种可靠的模型,并对模型进行了验证。其中基于原子契合方式构建的模型为最佳预测模型(CoMFA r~2=0.945,q_(LOO)~2=0.657;CoMSIA r~2=0.952,q_(LOO)~2=0.671)。此模型进一步通过14个化合物组成的样本外测试集进行验证,结果由CoMFA和CoMSIA模型得到的测试集外部验证系数(r_(pred)~2)分别为0.751和0.854。其次,利用分子对接和分子动力学模拟研究了这些黄酮类衍生物和核因子-κ蛋白激酶(PDB ID:4G3D)之间的相互作用,结果表明CoMFA和CoMSIA的立体、静电、疏水等力场系数等高图与分子对接的结果相一致,而分子动力学模拟又进一步验证了分子对接的结果。这些研究有助于揭示抑制剂与蛋白酶之间的作用模式,为进一步的新型抗癌药物的理性设计提供有益的信息。
The traditional MLR,the new SMILES-based method,and CoMFA and CoMSIA of 3D-QSAR were employed for studying flavonoid derivatives as nuclear factor-kappa protein kinase inhibitors.Several reliable models were established,and those models were verified.Statistically significant model of ligand-based 3D-QSAR from the common substructure-based alignment exhibited the best predictive power(CoMFA r~2=0.945,q~2 =0.657;CoMSIA r~2=0.952,q~2=0.671).The model was further confirmed by analyzing 14 sets of compounds with diverse structure.The results showed high predictive r values of 0.751 for CoMFA and 0.854 for CoMSIA respectively.The molecular docking analysis revealed that both CoMFA and CoMSIA contour maps for steric,electrostatic,hydrophobic,and hydrogen- bonding interactions matched well.Molecular dynamics simulation was employed to further validate the docking results.This work may lead to a better understanding of the mechanism of action and aid to design novel and more potent anticancer drugs.
The traditional MLR,the new SMILES-based method,and CoMFA and CoMSIA of 3D-QSAR were employed for studying flavonoid derivatives as nuclear factor-kappa protein kinase inhibitors.Several reliable models were established,and those models were verified.Statistically significant model of ligand-based 3D-QSAR from the common substructure-based alignment exhibited the best predictive power(CoMFA r~2=0.945,q~2 =0.657;CoMSIA r~2=0.952,q~2=0.671).The model was further confirmed by analyzing 14 sets of compounds with diverse structure.The results showed high predictive r values of 0.751 for CoMFA and 0.854 for CoMSIA respectively.The molecular docking analysis revealed that both CoMFA and CoMSIA contour maps for steric,electrostatic,hydrophobic,and hydrogen- bonding interactions matched well.Molecular dynamics simulation was employed to further validate the docking results.This work may lead to a better understanding of the mechanism of action and aid to design novel and more potent anticancer drugs.
引文
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