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The structure of active opsin as a basis for identification of GPCR agonists by dynamic homology modelling and virtual screening assays
Author(s) -
Schneider Michael,
Wolf Steffen,
Schlitter Jürgen,
Gerwert Klaus
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.10.027
Subject(s) - g protein coupled receptor , virtual screening , inverse agonist , homology modeling , in silico , computational biology , chemistry , homology (biology) , opsin , ligand (biochemistry) , rhodopsin , receptor , agonist , drug discovery , bioinformatics , biology , biochemistry , amino acid , enzyme , retinal , gene
Most of the currently available G protein‐coupled receptor (GPCR) crystal structures represent an inactive receptor state, which has been considered to be suitable only for the discovery of antagonists and inverse agonists in structure‐based computational ligand screening. Using the β 2 ‐adrenergic receptor (B2AR) as a model system, we show that a dynamic homology model based on an “active” opsin structure without further incorporation of experimental data performs better than the crystal structure of the inactive B2AR in finding agonists over antagonists/inverse agonists. Such “active‐like state” dynamic homology models can therefore be used to selectively identify GPCR agonists in in silico ligand libraries.