q^2引导构象选择CoMFA方法研究HIV-1 RT抑制剂  

q^2 Guided Conformation Selection Approach of CoMFA for HIV-1 RT Inhibitors

作　　者：曾宝珊[1] 陈敏伯[1] 董喜成[1] 刘新泳[2] 

机构地区：[1]中国科学院上海有机化学研究所 [2]山东大学药学院药物化学研究所,济南250012

出　　处：《化学学报》2003年第7期1121-1128,共8页Acta Chimica Sinica

基　　金：中国科学院2002年度创新工程资助项目。

摘　　要：对未知受体结构的药物设计其主导方法CoMFA来说,柔性目标分子的多种构象造成了问题的复杂性.本文介绍交叉验证参数R^2(q^2)引导的构象选择CoMFA方法,选择化合物的最佳构象.将一组47个HIV-1 RT抑制剂进行有、无构象选择的CoMFA分析来作评价.根据化合物的活性、毒性、选择性指数(毒性/活性比)等实验数据构建得到的模型,其交叉验证参数q^2为0.7以上,非交叉验证的相应参数为0.94以上,最后,还经过试验集化合物验证该模型的预测能力,置信度(1-α)>0.99.Me comparative molecular field analysis (CoMFA) as a main type of drug design methods in the case of unknown 3D structures of the receptor is now facing complexity due, to the existence of many conformations for flexible target molecules. A cross-validated R-2(q(2)) guided conformation selection approach of CoMFA studies was proposed. As an example, a set of 47 HfV-1 RT inhibitors was investigated by this. approach. In comparison with. the conventional CoMFA, the result of the conformation selection approach for prediction of activity, toxicity and selective index gave much better results with q(2) > 0.7 and the non-cross-validated R-2 > 0.94. At last, this model was tested with a test set of 12 compounds showing good prediction ability with confidence level (1 - alpha) > 0.99.

关 键 词：q^2引导构象选择 CoMFA方法 HIV-1RT抑制剂 比较分子场分析 配体药物 药物设计 

分 类 号：TQ460[化学工程—制药化工]