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Molecules 2017, 22(6), 959; doi:10.3390/molecules22060959

3D Pharmacophore-Based Virtual Screening and Docking Approaches toward the Discovery of Novel HPPD Inhibitors

1
Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin 150030, China
2
School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou 730000, China
*
Author to whom correspondence should be addressed.
Academic Editor: Alessandro Pedretti
Received: 29 April 2017 / Accepted: 5 June 2017 / Published: 9 June 2017
(This article belongs to the Section Theoretical Chemistry)
View Full-Text   |   Download PDF [12254 KB, uploaded 9 June 2017]   |  

Abstract

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. View Full-Text
Keywords: HPPD inhibitors; pharmacophore model; molecule docking; HipHop model; virtual screening; ChemDiv HPPD inhibitors; pharmacophore model; molecule docking; HipHop model; virtual screening; ChemDiv
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MDPI and ACS Style

Fu, Y.; Sun, Y.-N.; Yi, K.-H.; Li, M.-Q.; Cao, H.-F.; Li, J.-Z.; Ye, F. 3D Pharmacophore-Based Virtual Screening and Docking Approaches toward the Discovery of Novel HPPD Inhibitors. Molecules 2017, 22, 959.

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