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 anti- 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.

Key words: MOLECULAR DESIGN, BIOLOGICAL ACTIVITY, SELECTION, COMPUTER APPLICATIONS