4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is a potent new bleaching herbicide target. Therefore, in silico structure-based virtual screening was performed in order to speed up the identification of promising HPPD inhibitors. In this study, an integrated virtual screening protocol by combining 3D-pharmacophore model, molecular docking and molecular dynamics (MD) simulation was established to find novel HPPD inhibitors from four commercial databases. 3D-pharmacophore Hypo1 model was applied to efficiently narrow potential hits. The hit compounds were subsequently submitted to molecular docking studies, showing four compounds as potent inhibitor with the mechanism of the Fe(II) coordination and interaction with Phe360, Phe403, and Phe398. MD result demonstrated that nonpolar term of compound 3881 made great contributions to binding affinities. It showed an IC50 being 2.49 μM against AtHPPD in vitro. The results provided useful information for developing novel HPPD inhibitors, leading to further understanding of the interaction mechanism of HPPD inhibitors.

p-Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking-based virtual screening were performed to identify novel potential HPPD inhibitors. The complex-based pharmacophore model (CBP) with 0.721 of ROC used for screening compounds showed remarkable ability to retrieve known active ligands from among decoy molecules. The ChemDiv database was screened using CBP-Hypo2 as a 3D query, and the best-fit hits subjected to molecular docking with two methods of LibDock and CDOCKER in Accelrys Discovery Studio 2.5 (DS 2.5) to discern interactions with key residues at the active site of HPPD. Four compounds with top rankings in the HipHop model and well-known binding model were finally chosen as lead compounds with potential inhibitory effects on the active site of target. The results provided powerful insight into the development of novel HPPD inhibitors herbicides using computational techniques.

p-Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking based virtual screening were performed to identify novel potential HPPD inhibitors. The complex based pharmacophore model (CBP) with 0.721 of ROC used for screening compound showed remarkable ability to retrieve known active ligands from decoy molecule. The ChemDiv database was screened using CBP-Hypo2 as a 3D query, and the best-fit hits subjected to molecular docking with two methods of LibDock and CDOCKER in Accelrys Discovery Studio 2.5(DS 2.5) to discern interactions with key residues at the active site of HPPD. 4 Compounds with top rank in HipHop model and well-known binding model were finally chosen as identification of lead compounds with potentially inhibitory effects on active site of target. The results provided powerful insight to the development of novel HPPD inhibitors herbicides using computational techniques.

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Herbicide safener, a diverse group of chemicals, is an important tool used to protect plants from herbicidal injury. With the aim of decreasing drift injury of haloxyfop-P-methyl to sensitive plants, the protective effect of four safeners (R-28725, 3-dichloroacetyl oxazolidine and its two optical isomers) was evaluated. Physiological and biochemical tests were conducted under laboratory conditions in Northeast Agricultural University, China, by using seed treatment with safener and soil treatment with haloxyfop-P-methyl, respectively. The maize seeds treated with these safeners were safe from haloxyfop-P-methyl treatment. A positive correlation between growth level and endogenous glutathione (GSH) content, glutathione S-transferases (GST) activity was observed in this research. Enhancement of GSH content, GST activity and affinity of GST to 1-chloro-2,4-dinitrobenzene (CDNB) in maize treated by R-28725 was maximum. However, the detoxification of herbicide was not accompanied by the increase of acetyl-CoA-carboxylase (ACC) activity in maize.