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

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.