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Journal of Molecular Modeling

, Volume 15, Issue 9, pp 1145–1153 | Cite as

Homology modeling of human α1β2γ2 and house fly β3 GABA receptor channels and Surflex-docking of fipronil

  • Jin Cheng
  • Xiu-Lian Ju
  • Xiang-Yang Chen
  • Gen-Yan Liu
Original Paper

Abstract

To further explore the mechanism of selective binding of the representative γ-aminobutyric acid receptors (GABARs) noncompetitive antagonist (NCA) fipronil to insect over mammalian GABARs, three-dimensional models of human α1β2γ2 and house fly β3 GABAR were generated by homology modeling, using the cryo-electron microscopy structure of the nicotinic acetylcholine receptor (nAChR) of Torpedo marmorata as a template. Fipronil was docked into the putative binding site of the human α1β2γ2 and house fly β3 receptors by Surflex-docking, and the calculated docking energies are in agreement with experimental results. The GABA receptor antagonist fipronil exhibited higher potency with house fly β3 GABAR than with human α1β2γ2 GABAR. Furthermore, analyses of Surflex-docking suggest that the H-bond interaction of fipronil with Ala2 and Thr6 in the second transmembrane segment (TM2) of these GABARs plays a relatively important role in ligand selective binding. The different subunit assemblies of human α1β2γ2 and house fly β3 GABARs may result in differential selectivity for fipronil.

Keywords

Homology modeling Human α1β2γ2 GABAA receptor House fly β3 GABA receptor Surflex-docking Fipronil Selectivity 

Notes

Acknowledgment

This study was supported by National Natural Science Foundation of China; contract/grant number: 20572084

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jin Cheng
    • 1
  • Xiu-Lian Ju
    • 1
  • Xiang-Yang Chen
    • 2
  • Gen-Yan Liu
    • 1
  1. 1.School of Chemical Engineering & Pharmacy, Key Laboratory for Green Chemical Process of Ministry of EducationWuhan Institute of TechnologyWuhanPeople’s Republic of China
  2. 2.School of Computer Science and EngineeringWuhan Institute of TechnologyWuhanPeople’s Republic of China

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