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dc.contributor.authorShang, Chengen
dc.contributor.authorWhittleston, Chris Sen
dc.contributor.authorSutherland-Cash, Kyle Hen
dc.contributor.authorWales, Daviden
dc.date.accessioned2015-05-26T11:48:07Z
dc.date.available2015-05-26T11:48:07Z
dc.date.issued2015-03-24en
dc.identifier.citationShang et al. Journal of Chemical Theory and Computation (2015), 11 (5), pp 2307-2314. DOI: 10.1021/ct5010565en
dc.identifier.issn1549-9618
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/247970
dc.description.abstractIn 2009, the D222G mutation in the hemagglutinin (HA) glycoprotein of pandemic H1N1 influenza A virus was found to correlate with fatal and severe human infections. Previous static structural analysis suggested that, unlike the H1N1 viruses prevalent in 1918, the mutation did not compromise binding to human α2,6-linked glycan receptors, allowing it to transmit efficiently. Here we investigate the interconversion mechanism between two predicted binding modes in both 2009 and 1918 HAs, introducing a highly parallel intermediate network search scheme to construct kinetically relevant pathways efficiently. Accumulated mutations at positions 183 and 224 that alter the size of the binding pocket are identified with the fitness of the 2009 pandemic virus carrying the D222G mutation. This result suggests that the pandemic H1N1 viruses could gain binding affinity to the α2,3-linked glycan receptors in the lungs, usually associated with highly pathogenic avian influenza, without compromising viability.
dc.description.sponsorshipThis work was supported by the ERC and the EPSRC.
dc.languageEnglishen
dc.language.isoenen
dc.publisherACS
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.titleAnalysis of the contrasting pathogenicities induced by the D222G mutation in 1918 and 2009 pandemic influenza A virusesen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from ACS via http://pubs.acs.org/doi/abs/10.1021/ct5010565.en
prism.endingPage2314
prism.publicationDate2015en
prism.publicationNameJournal of Chemical Theory and Computationen
prism.startingPage2307
prism.volume11en
dc.rioxxterms.funderEPSRC
rioxxterms.versionofrecord10.1021/ct5010565en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-03-24en
dc.contributor.orcidWales, David [0000-0002-3555-6645]
dc.identifier.eissn1549-9626
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEuropean Research Council (267369)
pubs.funder-project-idEPSRC (EP/I001352/1)
rioxxterms.freetoread.startdate2016-03-24


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales