title: Solid-state NMR and MD simulations of the antiviral drug amantadine solubilized in DMPC bilayers.
abstract: The interactions of (15)N-labeled amantadine, an antiinfluenza A drug, with DMPC bilayers were investigated by solid-state NMR and by a 12.6-ns molecular dynamics (MD) simulation. The drug was found to assume a single preferred orientation and location when incorporated in these bilayers. The experimental and MD computational results demonstrate that the long axis of amantadine is on average parallel to the bilayer normal, and the amine group is oriented toward the headgroups of the lipid bilayers. The localization of amantadine was determined by paramagnetic relaxation and by the MD simulation showing that amantadine is within the interfacial region and that the amine interacts with the lipid headgroup and glycerol backbone, while the hydrocarbon portion of amantadine interacts with the glycerol backbone and much of the fatty acyl chain as it wraps underneath the drug. The lipid headgroup orientation changes on drug binding as characterized by the anisotropy of (31)P chemical shielding and (14)N quadrupolar interactions and by the MD simulation.
authors: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32310, USA.
authors: Conggang
authors: C
authors: Li
authors: Myunggi
authors: M
authors: Yi
authors: Jun
authors: J
authors: Hu
authors: Huan-Xiang
authors: HX
authors: Zhou
authors: Timothy A
authors: TA
authors: Cross
mesh_terms: D000547:Amantadine / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry; D003198:Computer Simulation; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008560:Membrane Fluidity; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D016062:Porosity; D012995:Solubility
chemical_list: D000998:Antiviral Agents; D008051:Lipid Bilayers; D000547:Amantadine; D004134:Dimyristoylphosphatidylcholine