01993nas a2200253   4500008004100000022001400041245013100055210006900186260001200255300001600267490000700283520117700290653001301467653002201480653003501502653004801537653001601585653002001601100001501621700001701636700002101653700001701674856004801691       2009                        eng d  a0948-502300aHomology modeling of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABA receptor channels and Surflex-docking of fipronil.0 aHomology modeling of human alpha 1 beta 2 gamma 2 and house fly   c09/2009  a1145–11530 v153 aTo further explore the mechanism of selective binding of the representative gamma-aminobutyric acid receptors (GABARs) noncompetitive antagonist (NCA) fipronil to insect over mammalian GABARs, three-dimensional models of human alpha 1 beta 2 gamma 2 and house fly beta 3 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 alpha 1 beta 2 gamma 2 and house fly beta 3 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 beta 3 GABAR than with human alpha 1 beta 2 gamma 2 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 alpha 1 beta 2 gamma 2 and house fly beta 3 GABARs may result in differential selectivity for fipronil.10afipronil10ahomology modeling10ahouse fly beta 3 GABA receptor10ahuman alpha 1 beta 2 gamma 2 GABAA receptor10aselectivity10asurflex-docking1 aCheng, Jin1 aJu, Xiu-Lian1 aChen, Xiang Yang1 aLiu, Gen-Yan  uhttp://www.ncbi.nlm.nih.gov/pubmed/19238461