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Front. Chem. | doi: 10.3389/fchem.2019.00556

QSAR Studies and Molecular Dynamics Simulations of 2-(Aryloxyacetyl)cyclohexane-1,3-diones Derivatives as HPPD Inhibitors

 Ying Fu1,  Yong-Xuan Liu1, Ke-Han Yi1, Ming-Qing Li1,  Jia-Zhong Li2 and  Fei Ye1*
  • 1Northeast Agricultural University, China
  • 2Lanzhou University, China

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a significant enzyme in the biosynthesis of plastoquinone and tocopherol, moreover, it is also potential target to develop new herbicide. The computer-aided drug design (CADD) was employed to the efficient discovery of new HPPD inhibitors in this study. Forty-three compounds with known activities were used to generate CoMFA and CoMSIA models based on common framework and molecular docking. The structural contribution to the activity was determined which provided further information for the design of novel inhibitors. Molecular docking was used to explain the changes in activity caused by the binding mode between ligand and protein. The molecular dynamics (MD) results indicated that the electrostatic energy was the major driving force for ligand-protein interaction and the Phe403 made the greatest contribution to the binding. The present work provided useful information for the rational design of novel HPPD inhibitors with improved activity.

Keywords: HPPD inhibitors, 3D-QSAR (three-dimensional quantitative structure activity relationship), molecular docking, Molecular dynamics (MD), MM-PBSA

Received: 02 Nov 2018; Accepted: 22 Jul 2019.

Edited by:

Ramon Carbó-Dorca, University of Girona, Spain

Reviewed by:

Guangfu Yang, Central China Normal University, China
Andrey A. Toropov, Dipartimento di Scienze della Salute Ambientale, Istituto Di Ricerche Farmacologiche Mario Negri (IRCCS), Italy
Elena Cichero, University of Genoa, Italy
Euzebio G. Barbosa, Federal University of Rio Grande do Norte, Brazil  

Copyright: © 2019 Fu, Liu, Yi, Li, Li and Ye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Fei Ye, Northeast Agricultural University, Harbin, China, yefei@neau.edu.cn