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dc.creatorZauhar, RJ
dc.creatorGianti, E
dc.creatorWelsh, WJ
dc.date.accessioned2021-01-31T18:19:21Z
dc.date.available2021-01-31T18:19:21Z
dc.date.issued2013-12-01
dc.identifier.issn0920-654X
dc.identifier.issn1573-4951
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/5338
dc.identifier.other24366428 (pubmed)
dc.identifier.urihttp://hdl.handle.net/20.500.12613/5356
dc.description.abstractSince its introduction in 2003, the Shape Signatures method has been successfully applied in a number of drug design projects. Because it uses a ray-tracing approach to directly measure molecular shape and properties (as opposed to relying on chemical structure), it excels at scaffold hopping, and is extraordinarily easy to use. Despite its advantages, a significant drawback of the method has hampered its application to certain classes of problems; namely, when the chemical structures considered are large and contain heterogeneous ring-systems, the method produces descriptors that tend to merely measure the overall size of the molecule, and begin to lose selective power. To remedy this, the approach has been reformulated to automatically decompose compounds into fragments using ring systems as anchors, and to likewise partition the ray-trace in accordance with the fragment assignments. Subsequently, descriptors are generated that are fragment-based, and query and target molecules are compared by mapping query fragments onto target fragments in all ways consistent with the underlying chemical connectivity. This has proven to greatly extend the selective power of the method, while maintaining the ease of use and scaffold-hopping capabilities that characterized the original implementation. In this work, we provide a full conceptual description of the next generation Shape Signatures, and we underline the advantages of the method by discussing its practical applications to ligand-based virtual screening. The new approach can also be applied in receptor-based mode, where protein-binding sites (partitioned into subsites) can be matched against the new fragment-based Shape Signatures descriptors of library compounds. © 2013 The Author(s).
dc.format.extent1009-1036
dc.language.isoen
dc.relation.haspartJournal of Computer-Aided Molecular Design
dc.relation.isreferencedbySpringer Science and Business Media LLC
dc.subjectLigand-based drug design
dc.subjectFragment-based shape signatures
dc.subjectScaffold hopping
dc.subjectShape signatures
dc.subjectShape similarity
dc.subjectVirtual screening
dc.titleFragment-based Shape Signatures: A new tool for virtual screening and drug discovery
dc.typeArticle
dc.type.genreJournal Article
dc.relation.doi10.1007/s10822-013-9698-7
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.date.updated2021-01-31T18:19:17Z
refterms.dateFOA2021-01-31T18:19:21Z


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