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dc.contributor.authorPascolutti, Mauro
dc.contributor.authorCampitelli, Marc
dc.contributor.authorBao, Nguyen
dc.contributor.authorNgoc, Pham
dc.contributor.authorGorse, Alain-Dominique
dc.contributor.authorQuinn, Ronald J
dc.date.accessioned2017-05-03T12:36:30Z
dc.date.available2017-05-03T12:36:30Z
dc.date.issued2015
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0120942
dc.identifier.urihttp://hdl.handle.net/10072/101071
dc.description.abstractNatural products are universally recognized to contribute valuable chemical diversity to the design of molecular screening libraries. The analysis undertaken in this work, provides a foundation for the generation of fragment screening libraries that capture the diverse range of molecular recognition building blocks embedded within natural products. Physicochemical properties were used to select fragment-sized natural products from a database of known natural products (Dictionary of Natural Products). PCA analysis was used to illustrate the positioning of the fragment subset within the property space of the non-fragment sized natural products in the dataset. Structural diversity was analysed by three distinct methods: atom function analysis, using pharmacophore fingerprints, atom type analysis, using radial fingerprints, and scaffold analysis. Small pharmacophore triplets, representing the range of chemical features present in natural products that are capable of engaging in molecular interactions with small, contiguous areas of protein binding surfaces, were analysed. We demonstrate that fragment-sized natural products capture more than half of the small pharmacophore triplet diversity observed in non fragment-sized natural product datasets. Atom type analysis using radial fingerprints was represented by a self-organizing map. We examined the structural diversity of non-flat fragment-sized natural product scaffolds, rich in sp3 configured centres. From these results we demonstrate that 2-ring fragment-sized natural products effectively balance the opposing characteristics of minimal complexity and broad structural diversity when compared to the larger, more complex fragment-like natural products. These naturally-derived fragments could be used as the starting point for the generation of a highly diverse library with the scope for further medicinal chemistry elaboration due to their minimal structural complexity. This study highlights the possibility to capture a high proportion of the individual molecular interaction motifs embedded within natural products using a fragment screening library spanning 422 structural clusters and comprised of approximately 2800 natural products.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherPublic Library of Sciences
dc.relation.ispartofpagefrome0120942-1
dc.relation.ispartofpagetoe0120942-12
dc.relation.ispartofissue4
dc.relation.ispartofjournalPLoS One
dc.relation.ispartofvolume10
dc.subject.fieldofresearchComplementary and Alternative Medicine not elsewhere classified
dc.subject.fieldofresearchcode110499
dc.titleCapturing nature's diversity
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.description.versionPublished
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© 2015 Pascolutti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorQuinn, Ronald J.
gro.griffith.authorPham, Ngoc B.
gro.griffith.authorCampitelli, Marc R.
gro.griffith.authorPascolutti, Mauro
gro.griffith.authorNguyen, Bao
gro.griffith.authorGorse, Dominique


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