From the crystal structure of acetolactate synthase (ALS) or acetohydroxyacid synthase (AHAS), a docking study was performed to explore the binding modes of 8 sulfonylurea analogues to ALS as its inhibitors using combined DOCK5 and Autodock3 programs. On the basis of the modes and the crystal structure of ALS and sulfonylurea complex, a simplified pharmacophore was obtained. Accordingly, 425 known pesticides, which were not previously found to have the function of inhibiting ALS, were screened by the same docking methods. A number of molecules were found to have the function of inhibition to ALS. It was predicted that those molecules could be used as the inhibitor of ALS. This result revealed the structure-activity relationships of this kind of pesticide and can be used to design and synthesize novel lead compound as ALS inhibitors.

Key words: sulfonylurea, ALS/AHAS inhibitor, binding mode, docking, virtual screening