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dc.contributor.authorde Bruyn Kops, Christina
dc.contributor.authorStork, Conrad
dc.contributor.authorSicho, Martin
dc.contributor.authorKochev, Nikolay
dc.contributor.authorSvozil, Daniel
dc.contributor.authorJeliazkova, Nina
dc.contributor.authorKirchmair, Johannes
dc.date.accessioned2020-03-09T13:32:13Z
dc.date.available2020-03-09T13:32:13Z
dc.date.issued2019-06-12
dc.Publishedde Bruyn Kops C, Stork C, Sicho M, Kochev N, Svozil, Jeliazkova N, Kirchmair J. GLORY: Generator of the structures of likely cytochrome P450 metabolites based on predicted sites of metabolism. Frontiers in Chemistry. 2019;7:402eng
dc.identifier.issn2296-2646en_US
dc.identifier.urihttps://hdl.handle.net/1956/21459
dc.description.abstractComputational prediction of xenobiotic metabolism can provide valuable information to guide the development of drugs, cosmetics, agrochemicals, and other chemical entities. We have previously developed FAME 2, an effective tool for predicting sites of metabolism (SoMs). In this work, we focus on the prediction of the chemical structures of metabolites, in particular metabolites of xenobiotics. To this end, we have developed a new tool, GLORY, which combines SoM prediction with FAME 2 and a new collection of rules for metabolic reactions mediated by the cytochrome P450 enzyme family. GLORY has two modes: MaxEfficiency and MaxCoverage. For MaxEfficiency mode, the use of predicted SoMs to restrict the locations in the molecule at which the reaction rules could be applied was explored. For MaxCoverage mode, the predicted SoM probabilities were instead used to develop a new scoring approach for the predicted metabolites. With this scoring approach, GLORY achieves a recall of 0.83 and can predict at least one known metabolite within the top three ranked positions for 76% of the molecules of a new, manually curated test set. GLORY is freely available as a web server at https://acm.zbh.uni-hamburg.de/glory/, and the datasets and reaction rules are provided in the Supplementary Material.en_US
dc.language.isoengeng
dc.publisherFrontiersen_US
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0eng
dc.subjectmetabolism predictioneng
dc.subjectmetabolite structure predictioneng
dc.subjectrule-based approacheng
dc.subjectsites of metabolismeng
dc.subjectxenobiotic metabolismeng
dc.subjectcytochrome P450eng
dc.subjectmetaboliteseng
dc.titleGLORY: Generator of the structures of likely cytochrome P450 metabolites based on predicted sites of metabolismen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2020-02-12T09:47:05Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2019 The Author(s)en_US
dc.identifier.doihttps://doi.org/10.3389/fchem.2019.00402/abstract
dc.identifier.cristin1748215
dc.source.journalFrontiers in Chemistry
dc.relation.projectTrond Mohn stiftelse: BFS2017TMT01


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