喜树碱及其衍生物的比较分子力场分析(CoMFA)研究

Comparative Moleculer Field Analysis(CoMFA) of Camptothecin Analogs

采用最小二乘匹配和场匹配两种不同叠合规则,以sp3C+ ,sp3 O0-4 - 和sp3O2 - 3 种不同探针对喜树碱类化合物进行了比较分子力场分析法(CoMFA) 研究,并对CoMFA 中降低静电势的选项及偏最小二乘法(PLS) 分析中的比例调整方法选项的设置进行了比较.对所得较佳模型进行网格空间的系统平移获得了有更强预测能力的三维定量构效关系(3DQSAR) 模型,并成功地对检验组化合物作了活性预测.通过对模型的势场图分析,获得了该类化合物与受体相互作用的大量信息。

Comparative molecular field analysis(CoMFA)using three different probes has been used to establish 3D QSAR models of camptothecin analogs which were aligned by two different alignment rules:rms Fit and Field Fit.And the settings of Drop Electrostatics in CoMFA option and the Scaling method in PLS option were studied too.To the resultant good models,the Region′s systemic moving was enforced and the best models were obtained and their powerful predictive abilities were proved by predicting ten camptothecin analogs in the test set.By analyzing the contour plots of CoMFA models,a lot of information about the interaction between the CPT and receptor was obtained,which would be in favour of designing the novel high potent analogs.