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dc.contributor.authorPerez-Nueno, Violeta I.
dc.contributor.authorVenkatraman, Vishwesh
dc.contributor.authorMavridis, Lazaros
dc.contributor.authorRitchie, David W.
dc.date.accessioned2012-07-25T00:02:55Z
dc.date.available2012-07-25T00:02:55Z
dc.date.issued2011
dc.identifier.citationPerez-Nueno , V I , Venkatraman , V , Mavridis , L & Ritchie , D W 2011 , ' Predicting drug promiscuity using spherical harmonic surface shape-based similarity comparisons ' , The Open Conference Proceedings Journal , vol. 2 , pp. 113-129 . https://doi.org/10.2174/2210289201102010113en
dc.identifier.issn2210-2892
dc.identifier.otherPURE: 16716285
dc.identifier.otherPURE UUID: 24269a93-ef7e-440b-9e4f-80407d188c53
dc.identifier.urihttps://hdl.handle.net/10023/3009
dc.description.abstractPolypharmacology is becoming an increasingly important aspect in drug design. Pharmaceutical companies are discovering more and more cases in which multiple drugs bind to a given target (promiscuous targets) and in which a given drug binds to more than one target (promiscuous ligands). These phenomena are clearly of great importance when considering drug side-effects. In the last 4 years, more than 30 drugs have been tested against more than 40 novel secondary targets based on promiscuity predictions. Current methods for predicting promiscuity typically aim to relate protein receptors according to their primary sequences, the similarity of their ligands, and more recently, the similarity of their ligand binding pockets. Here, we present a spherical harmonic (SH) surface shape-based approach to predict rapidly promiscuous ligands and targets by comparing sets of SH ligand and protein shapes, respectively. We present details of our approach applied to a wide range of PDB complexes comprising ligands in a selected subset of the MDL Drug Data Report (MDDR) database which are distributed over 249 diverse pharmacological targets. The shape similarity of each ligand to each target’s ligand set is quantified and used to predict promiscuity. We also analyse the correlation between binding pocket and ligand shapes. We compare our promiscuity predictions with experimental activity values extracted from the BindingDB database.
dc.language.isoeng
dc.relation.ispartofThe Open Conference Proceedings Journalen
dc.rights© Pérez-Nueno et al.; Licensee Bentham Open. This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.en
dc.subjectConsensus shapesen
dc.subjectDrug promiscuityen
dc.subjectLigand shape spaceen
dc.subjectProtein pocket spaceen
dc.subjectProtein sequence spaceen
dc.subjectShape similarityen
dc.subjectSpherical harmonic shapesen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subject.lccRMen
dc.titlePredicting drug promiscuity using spherical harmonic surface shape-based similarity comparisonsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.identifier.doihttps://doi.org/10.2174/2210289201102010113
dc.description.statusPeer revieweden
dc.date.embargoedUntil2012-07-25


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