摘要
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rc2v=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.
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 rCV^2 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.
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2006年第13期1373-1378,共6页
Acta Chimica Sinica
基金
国家重点基础研究发展计划(No.2003CB114406)
科技部国际合作重点(No.2004DFA01500)资助项目.
关键词
KARI酶
分子对接
三维定量构效关系
KARI
molecular docking
three-dimensional quantitative structure-activity relationship
