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化学学报
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化学学报 ›› 2006, Vol. 64 ›› Issue (13): 1373-1378. 上一篇    下一篇

研究论文

脒类KARI酶抑制剂的分子对接和3D-QSAR研究

王宝雷，王建国，马翼，李正名*，李永红，王素华   

  1. (南开大学元素有机化学研究所元素有机化学国家重点实验室 天津 300071)
  • 投稿日期:2005-09-14 修回日期:2006-03-09 发布日期:2006-07-14
  • 通讯作者: 李正名

Molecular Docking and 3D-QSAR Research of Amidines of KARI Inhibitor

WANG Bao-Lei, WANG Jian-Guo, MA Yi, LI Zheng-Ming*, LI Yong-Hong, WANG Su-Hua   

  1. (National Key Laboratory of Elemento-Organic Chemistry, Institue of Elemento-Organic Chemistry,
    Nankai University, Tianjin 300071)
  • Received:2005-09-14 Revised:2006-03-09 Published:2006-07-14
  • Contact: LI Zheng-Ming

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被引次数

49 | 10

对设计合成的20个单脒类化合物的水稻KARI酶体外抑制活性和体内除草活性进行了分子对接和三维定量构效关系研究. 前者采用AutoDock3.0方法, 研究发现化合物活性变化趋势与分子对接计算结果基本一致, 通过分析化合物9与KARI酶活性氨基酸残基结合模式发现, 残基Glu319, Asp315, Glu496, Gly253, Met254, Cys517等对氢键和静电相互作用以及疏水作用都有重要贡献; 后者研究采用比较分子力场分析(CoMFA)方法, 结果表明立体场和静电场对活性的贡献分别为67.8%和32.2%, 交叉验证系数rcv2＝0.774, 非交叉验证r2＝0.999, F＝1593.134, 标准偏差s＝0.036, 所建立的3D-QSAR模型对化合物除草活性具有较好的预测能力. 两种方法研究结果为进一步设计合成更高活性的KARI酶抑制剂提供了指导.

关键词: KARI酶, 分子对接, 三维定量构效关系

The molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) of 20 monoamidine compounds synthesized were studied according to their rice KARI inhibitory (in vitro) and herbicidal (in vivo) activity. For the former, an AutoDock3.0 method was used. It was found that the trend of activity change of compounds is accordant with the results from AutoDock calculations. The binding pattern of compound 9 with KARI active residues was also analyzed, and the result shows that several residues (Glu319, Asp315, Glu496, Gly253, Met254, Cys517, etc.) have very important effect on hydrogen bond, electrostatic and hydrophobic interactions. For the latter, the comparative molecular field analysis (CoMFA) was adopted. The result shows that the contributions of steric and electrostatic fields to the activity are 67.8% and 32.2% respectively. The cross-validated rcv2 and the relation coefficient r2 for the model established are 0.774 and 0.999 respectively, with the F value of 1593.134 and the standard deviation (s) of 0.036. The result indicates that the 3D-QSAR model is significant and has good predictability. The research results provided useful guidance for designing more potent KARI inhibitors prior to their synthesis.

Key words: KARI, molecular docking, three-dimensional quantitative structure-activity relationship