title: Interaction of aminoadamantane derivatives with the influenza A virus M2 channel-docking using a pore blocking model.
abstract: Interaction of aminoadamantanes with the influenza A virus M2 proton channel was analyzed by docking simulations of a series of synthetic aminoadamantane derivatives, of differing binding affinity, into the crystal structure of the transmembrane (M2TM) pore. The pore blocking model tested in the 'gas phase' describes qualitatively the changes on the relative binding affinities of the compounds (although a series of highly hydrophobic ligands which seem to have little capacity for different specific interactions with their receptor). The docking calculations predicted poses in which the adamantane ring is surrounded mainly by the alkyl side chains of Val27 or Ala30 and the ligand's amino group is generally hydrogen bonded with hydroxyls of Ser31 or carbonyls of Val27 or carbonyls of Ala30, the former (Ser31) being the most stable and most frequently observed. The binding of the ligand is a compromise between hydrogen bonding ability, which is elevated by a primary amino group, and apolar interactions, which are increased by the ability of the lipophilic moiety to adequately fill a hydrophobic pocket within the M2TM pore. A delicate balance of these hydrophobic contributions is required for optimal interaction.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupolis-Zografou, 15771 Athens, Greece.
authors.forename: Stelios
authors.initials: S
authors.lastname: Eleftheratos
authors.forename: Philip
authors.initials: P
authors.lastname: Spearpoint
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ortore
authors.forename: Antonios
authors.initials: A
authors.lastname: Kolocouris
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
authors.forename: Stephen
authors.initials: S
authors.lastname: Martin
authors.forename: Alan
authors.initials: A
authors.lastname: Hay
mesh_terms: D000218:Adamantane / Q000737:chemistry*; D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014763:Viral Matrix Proteins / Q000737:chemistry*; D000086082:Viroporin Proteins
chemical_list: D000218:Adamantane; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins