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dc.contributor.authorForrest, L. R.
dc.contributor.authorKukol, A.
dc.contributor.authorArkin, I.T.
dc.contributor.authorTieleman, D. P.
dc.contributor.authorSansom, M. S. P.
dc.date.accessioned2011-10-18T10:01:12Z
dc.date.available2011-10-18T10:01:12Z
dc.date.issued2000-01
dc.identifier.citationForrest , L R , Kukol , A , Arkin , I T , Tieleman , D P & Sansom , M S P 2000 , ' Exploring models of the influenza A M2 channel: MD simulations in a phospholipid bilayer ' , Biophysical Journal , vol. 78 , no. 1 , pp. 55-69 . https://doi.org/10.1016/S0006-3495(00)76572-6
dc.identifier.issn0006-3495
dc.identifier.otherPURE: 420760
dc.identifier.otherPURE UUID: 8453ee2b-6dc1-4887-96bb-b4390becaf72
dc.identifier.otherWOS: 000084772900006
dc.identifier.otherScopus: 0034030929
dc.identifier.urihttp://hdl.handle.net/2299/6694
dc.description.abstractThe M2 protein of influenza A virus forms homotetrameric helix bundles, which function as proton-selective channels. The native form of the protein is 97 residues long, although peptides representing the transmembrane section display ion channel activity, which (like the native channel) is blocked by the antiviral drug amantadine. As a small ion channel, M2 may provide useful insights into more complex channel systems. Models of tetrameric bundles of helices containing either 18 or 22 residues have been simulated while embedded in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphatidylcholine bilayer. Several different starting models have been used. These suggest that the simulation results, at least on a nanosecond time scale, are sensitive to the exact starting structure. Electrostatics calculations carried out on a ring of four ionizable aspartate residues at the N-terminal mouth of the channel suggest that at any one time, only one will be in a charged state. Helix bundle models were mostly stable over the duration of the simulation, and their helices remained tilted relative to the bilayer normal. The M2 helix bundles form closed channels that undergo breathing motions, alternating between a tetramer and a dimer-of-dimers structure. Under these conditions either the channel forms a pocket of trapped waters or it contains a column of waters broken predominantly at the C-terminal mouth of the pore. These waters exhibit restricted motion in the pore and are effectively "frozen" in a way similar to those seen in previous simulations of a proton channel formed by a four-helix bundle of a synthetic leucine-serine peptide.en
dc.format.extent15
dc.language.isoeng
dc.relation.ispartofBiophysical Journal
dc.subjectMOLECULAR-DYNAMICS SIMULATIONS
dc.subjectM(2) ION-CHANNEL
dc.subjectA VIRUS
dc.subjectTRANSMEMBRANE DOMAIN
dc.subjectMEMBRANE-PROTEINS
dc.subjectGRAMICIDIN-A
dc.subjectPROTON-TRANSFER
dc.subjectWATER
dc.subjectSELECTIVITY
dc.subjectPHOSPHATIDYLCHOLINE
dc.titleExploring models of the influenza A M2 channel: MD simulations in a phospholipid bilayeren
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionAgriculture, Veterinary and Food Sciences
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionCardiovascular Pathologies
dc.contributor.institutionBiochemistry and Bioinformatics
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dcterms.dateAccepted2000-01
rioxxterms.versionofrecordhttps://doi.org/10.1016/S0006-3495(00)76572-6
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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