Molecular Modeling and Molecular Dynamics Simulation of the Human A2B Adenosine Receptor. The Study of the Possible Binding Modes of the A2B Receptor Antagonistsстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
Аннотация:A molecular model of the human A2B adenosine receptor containing seven transmembrane α helices connected by three intracellular and three extracellular hydrophilic loops had been constructed. A molecular docking of seven structurally diverse xanthine antagonists of the A2B receptor was performed, and the differences in their binding modes were investigated. The 1 ns molecular dynamics (MD) simulations of several obtained ligand−receptor complexes inserted into the phospholipid bilayer were carried out. The conformational changes of the A2B receptor occurring during MD simulations were explored, and the stable binding modes of the studied antagonists were determined. According to the models presented in this work, the involvement of the His251, Asn282, Ser92, Thr89, and some aromatic residues in ligand recognition was determined. The obtained binding modes of the A2B antagonists demonstrate good agreement with the site-directed mutagenesis data.