一种新的De Novo生物活性分子设计方法  

A New Method for De Novo Bio-active Molecular Design

作　　者：陈海峰[1] 谷妍[1] 董喜城[1] 荔建锋[1] 张世相[1] 袁身刚[1] 陈敏伯[1] 郑崇直[1] 

机构地区：[1]中国科学院上海有机化学研究所计算机化学开放实验室,上海200032

出　　处：《化学学报》2000年第9期1168-1172,共5页Acta Chimica Sinica

基　　金：国家科技部"九五"重点攻关项目;国家基础研究发展规划和中法先进研究计划;国家自然科学基金重点项目;国家自然科学基金(29872048);国家教委留学回国人员科研基金;上海市科技开发基金;国家高性能计算基金

摘　　要：由药效团进行虚拟活性结构生成与3D-QSAR模型相结合,筛选出有前途的结构多样性的化合物,并从中寻找活性先导化合物,是一种新的分子设计方法.采用这种方法对抗小麦赤霉病类含氟农药进行了研究,共生成了53个虚拟活性结构,通过3D-QSAR模型筛选出其中10个活性较高的结构,在活性最高的化合物基础上进行了结构修饰,得到了活性更高巨毒性较低的理想化合物.研究结果表明这种方法能突破原模型化合物结构模式的局限,可以找到结构新颖的活性先导化合物,是一种非常有前途的分子设计方法,而且具有较高的筛选效率.A new De Novo method for bio - active molecular design is presented, which combines virtual bio -active structural generation with 3D - QSAR study. This method could generate a lot of highly diverse molecules and find bio - active lead compounds. The method is illustrated through a study on a set of fluorine - containing pesticides for and - gibberella. With the constraints of the pharmacophore obtained by DISCO, 53 virtual bio - active structures were generated, and their anti - gibberella activities were predicted by CoMFA. The 10 most active compounds were selected and screened by 3D - QSAR. The first one was investigated in depth by modifying and simplifying its structure. The results showed that the method was a feasible means for bio - active molecular design. It had high screen efficiency.

关 键 词：3D-QSAR DeNovo 含氟农药 分子设计 药效团 

分 类 号：TQ450[化学工程—农药化工]