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dc.contributor.authorLandon, Melissa R.en_US
dc.contributor.authorAmaro, Rommie E.en_US
dc.contributor.authorBaron, Riccardoen_US
dc.contributor.authorNgan, Chi Hoen_US
dc.contributor.authorOzonoff, Daviden_US
dc.contributor.authorAndrew McCammon, J.en_US
dc.contributor.authorVajda, Sandoren_US
dc.date.accessioned2011-12-29T22:48:41Z
dc.date.available2011-12-29T22:48:41Z
dc.date.issued2011-12-29
dc.identifier.citationLandon, Melissa R, Rommie E Amaro, Riccardo Baron, Chi Ho Ngan, David Ozonoff, J Andrew McCammon, Sandor Vajda. "Novel Druggable Hot Spots in Avian Influenza Neuraminidase H5N1 Revealed by Computational Solvent Mapping of a Reduced and Representative Receptor Ensemble" Chemical Biology & Drug Design 71(2):106-116. (2008)
dc.identifier.issn1747-0285
dc.identifier.urihttp://hdl.handle.net/2144/2605
dc.description.abstractThe influenza virus subtype H5N1 has raised concerns of a possible human pandemic threat because of its high virulence and mutation rate. Although several approved anti-influenza drugs effectively target the neuraminidase, some strains have already acquired resistance to the currently available anti-influenza drugs. In this study, we present the synergistic application of extended explicit solvent molecular dynamics (MD) and computational solvent mapping (CS-Map) to identify putative 'hot spots' within flexible binding regions of N1 neuraminidase. Using representative conformations of the N1 binding region extracted from a clustering analysis of four concatenated 40-ns MD simulations, CS-Map was utilized to assess the ability of small, solvent-sized molecules to bind within close proximity to the sialic acid binding region. Mapping analyses of the dominant MD conformations reveal the presence of additional hot spot regions in the 150- and 430-loop regions. Our hot spot analysis provides further support for the feasibility of developing high-affinity inhibitors capable of binding these regions, which appear to be unique to the N1 strain.en_US
dc.description.sponsorshipNational Institutes of Health (R01-HM064700, F32-GM077729, GM31749); National Science Foundation (CHE060073N, MCB-0506593, MCA93S013); Howard Hughes Medical Institute; San Diego Supercomputing Center, Accelrys, Inc.; W.M. Keck Foundation; National Biomedical Computational Resource Center for Theoretical Biological Physicsen_US
dc.language.isoenen_US
dc.publisherBlackwell Publishing Ltden_US
dc.subjectComputational solvent mappingen_US
dc.subjectEnsemble-based drug designen_US
dc.subjectH5N1en_US
dc.subjectHot spoten_US
dc.subjectMolecular dynamicsen_US
dc.subjectNeuraminidaseen_US
dc.subjectReceptor flexibilityen_US
dc.subjectRMSD clusteringen_US
dc.titleNovel Druggable Hot Spots in Avian Influenza Neuraminidase H5N1 Revealed by Computational Solvent Mapping of a Reduced and Representative Receptor Ensembleen_US
dc.typearticleen_US
dc.identifier.doi10.1111/j.1747-0285.2007.00614.x
dc.identifier.pubmedid18205727
dc.identifier.pmcid2438278


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