title: Molecular modeling and molecular dynamics simulation of the human A2B adenosine receptor. The study of the possible binding modes of the A2B receptor antagonists.
abstract: A molecular model of the human A(2B) adenosine receptor containing seven transmembrane alpha helices connected by three intracellular and three extracellular hydrophilic loops had been constructed. A molecular docking of seven structurally diverse xanthine antagonists of the A(2B) 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 A(2B) 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 A(2B) antagonists demonstrate good agreement with the site-directed mutagenesis data.
authors.affiliation: Department of Chemistry, M. V. Lomonosov Moscow State University, 119992 Moscow, Russian Federation.
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Ivanov
authors.forename: Igor I
authors.initials: II
authors.lastname: Baskin
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Palyulin
authors.forename: Laura
authors.initials: L
authors.lastname: Piccagli
authors.forename: Pier G
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Nikolai S
authors.initials: NS
authors.lastname: Zefirov
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010743:Phospholipids / Q000737:chemistry; D043704:Receptor, Adenosine A2B / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D008051:Lipid Bilayers; D010743:Phospholipids; D043704:Receptor, Adenosine A2B; D014867:Water