Molecular interactions between fenoterol stereoisomers and derivatives and the β2-adrenergic receptor binding site studied by docking and molecular dynamics simulations

• DOI: 10.1007/s00894-013-1981-y
• Publication Date: 2013-09-16T02:04:45Z
• Authors: Anita Plazinska; Michal Kolinski; Irving W. Wainer; Krzysztof Jozwiak
• Keywords: Docking (animal); Fenoterol; Molecular model; Molecular Recognition

The β2 adrenergic receptor (β2-AR) has become a model system for studying the ligand recognition process and mechanism of G protein coupled receptors activation. In present study stereoisomers fenoterol some its derivatives (N = 94 molecules) were used as molecular probes to identify differences in stereo-recognition interactions between β2-AR structurally similar agonists. aimed at determining 3D models derivative-β2-AR complexes. Molecular have been developed by using crystal structure human T4 lysozyme fusion with bound (S)-carazolol (PDB ID: 2RH1) more recently reported nanobody-stabilized active state full agonist BI-167107 3P0G). docking procedure allowed us similarities binding site(s) tested ligands. molecules occupied same region, TM III, V, VI VII. residues identified during (Ser203, Ser207, Asp113, Lys305, Asn312, Tyr308, Asp192) experimentally indicated functional biophysical studies being very important agonist-receptor interactions. Moreover, additional space, an extension orthosteric pocket, was described. Furthermore, dynamics simulations interaction ligands ((R,R')- (S,S')-fenoterol) β2-AR. Our research offers new insights into stereoselective one most GPCR member. This may also facilitate design improved selective medications, which can be treat, prevent control heart failure symptoms.