The Structure-Based Three-Dimensional Pharmacophore Models for Arabidopsis thaliana HPPD inhibitors as Herbicide

Abstract

Division of Convergence Chemistry, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, KoreaReceived June 24, 2013, Accepted July 5, 2013p-Hydroxyphenylpyruvate dioxygenase (HPPD) is a potent herbicide target that is in current use. In this study,we developed a predictive pharmacophore model that uses known HPPD inhibitors based on a theoreticallyconstructed HPPD homology model. The pharmacophore model derived from the three-dimensional (3D)structure of a target protein provides helpful information for analyzing protein-ligand interactions, leading tofurther improvement of the ligand binding affinity.Key Words : HPPD, Herbicide, Pharmacophore, Molecular dockingIntroductionThe success rate for herbicidal discovery in agriculturalresearch has been decreasing in recent years. Thus, there isan urgent need for innovation in the area of herbicide dis-covery. Accordingly, a paramount goal for modern herbicideresearch is to discover a new potent target that severelydisrupts a plant’s metabolism by inhibiting essential enzymesfor growth. The successful design of a novel herbicidedepends on selectivity and safety issues. Selective herbicidetargets are usually single enzymes in plants with a conven-tional mode of action. By uniquely binding to the active siteof the target protein, the inhibition activity should affectunwanted weeds and thus protect agricultural products.Regarding the safety issue, the herbicide should follow stricttoxicity regulations to mitigate any harmful effects on humans.