Preprint Article Version 1 This version not peer reviewed

3D Pharmacophore-based Virtual Screening, Docking Approaches toward the Discovery of Novel HPPD Inhibitors

Version 1 : Received: 4 June 2017 / Approved: 5 June 2017 / Online: 5 June 2017 (05:16:39 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Molecules 2017, 22, 959
DOI: 10.3390/molecules22060959

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 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.

Subject Areas

HPPD inhibitors; pharmacophore model; molecule docking; HipHop model; virtual screening; ChemDiv

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