PUBLICATION

Binding Difference of Fipronil with GABAARs in Fruitfly and Zebrafish: Insights from Homology Modeling, Docking, and Molecular Dynamics Simulation Studies

Authors
Zheng, N., Cheng, J., Zhang, W., Li, W., Shao, X., Xu, Z., Xu, X., Li, Z.
ID
ZDB-PUB-141011-4
Date
2014
Source
Journal of Agricultural and Food Chemistry   62(44): 10646-53 (Journal)
Registered Authors
Zhang, Wei
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Drosophila/chemistry
  • Drosophila/genetics
  • Drosophila/metabolism*
  • Drosophila Proteins/chemistry*
  • Drosophila Proteins/genetics
  • Drosophila Proteins/metabolism
  • Hydrogen Bonding
  • Insecticides/chemistry*
  • Insecticides/metabolism
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Protein Binding
  • Pyrazoles/chemistry*
  • Pyrazoles/metabolism
  • Receptors, GABA-A/chemistry*
  • Receptors, GABA-A/metabolism
  • Sequence Alignment
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
25302733 Full text @ J. Agric. Food Chem.
Abstract
Fipronil, which targets on GABAA receptors (GABAARs), is the first phenylpyrazole insecticide widely used in crops protection and public hygiene. However, its high toxicity on fishes deeply limited its applications. In the present study, a series of computational methods including the homology modeling, docking and molecular dynamics simulation studies were integrated to explore the binding difference of fipronil with GABAARs from fruitfly and zebrafish systems. It was found that, in zebrafish system, the H-bond between 6'Thr and fipronil exerted key effects on the recognition of fipronil, which was absent in fruitfly system. On the other hand, in fruitfly system, strong electrostatic interaction between 2'Ala and fipronil was favorable to the binding of fipronil, while was detrimental to the binding in zebrafish system. These findings marked the binding difference of fipronil with different GABAARs, which might be helpful in designing selective insecticides against pests instead of fishes.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping