钠离子通道开放剂的药效团模型与构效关系研究  

Studies on the pharmacophore and 3D-QSAR of openers binding to sodium channel

作　　者：潘里[1] 丁晓琴[1] 丁俊杰[1] 李大禹[1] 陈冀胜[1] 

机构地区：[1]北京药物化学研究所,北京102205

出　　处：《计算机与应用化学》2015年第8期897-902,共6页Computers and Applied Chemistry

摘　　要：采用软件Catalyst的Hip Hop、Hypo Gen方法和Sybyl 6.5的Co MSIA方法,对作用于钠离子通道位点2的一些类似物进行三维药效团模型和三维定量构效关系研究。计算结果表明,构建的药效团模型相关系数为0.946727,Co MSIA模型的交叉验证相关系数(CV_r2)为0.739,方程的相关系数r2为0.981,两者均得到了较佳的预测模型。这些模型可用于对该作用位点的化合物进行作用机理探讨和活性评价,为进一步设计新农药和合成高效低毒的钠离子通道开放剂提供一些理论依据。In the paper, the Catalyst HipHop, HypoGen and Sybyl CoMSIA methods were applied to establish the 3D pharmacophore model, and the 3D-QSAR models of 15 analogs binding to site 2 of sodium channel. The builded pharmacophore（Correl=0.946727） and CoMSIA models with Cross-Validation regression coefficient（CV_r^2） value of 0.739 and correlation coefficient（r^2） of 0.986 were significant and have good predictability. The obtained results can be used to explain the structure and activity relationship, to predict activity, and moreover, to give insights to the further design and synthesize of the new sodium channel activator for pesticide. The interaction between the openers and sodium channel is very complicated. In the process of sodium channel combining with the openers, the conformational change of the ligand and the receptor is continuous. It is influenced by the micro-environment. Finally, sodium channel would stay in activated state continuously. For further research of the combining between sodium channel and the openers, homology modeling and molecular docking simulation are carrying out in our lab.

关 键 词：钠离子通道位点2类似物 catalyst药效团 比较分子相似性指数分析(CoMSIA) 三维定量构效关系(3D-QSAR) 

分 类 号：R914.2[医药卫生—药物化学]