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dc.creatorLapillo, M
dc.creatorTuccinardi, T
dc.creatorMartinelli, A
dc.creatorMacchia, M
dc.creatorGiordano, A
dc.creatorPoli, G
dc.date.accessioned2020-12-16T18:00:48Z
dc.date.available2020-12-16T18:00:48Z
dc.date.issued2019-03-01
dc.identifier.issn1661-6596
dc.identifier.issn1422-0067
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/4554
dc.identifier.other30818741 (pubmed)
dc.identifier.urihttp://hdl.handle.net/20.500.12613/4572
dc.description.abstract© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The development of target-fishing approaches, aimed at identifying the possible protein targets of a small molecule, represents a hot topic in medicinal chemistry. A successful target-fishing approach would allow for the elucidation of the mechanism of action of all therapeutically interesting compounds for which the actual target is still unknown. Moreover, target-fishing would be essential for preventing adverse effects of drug candidates, by predicting their potential off-targets, and it would speed up drug repurposing campaigns. However, due to the huge number of possible protein targets that a small-molecule might interact with, experimental target-fishing approaches are out of reach. In silico target-fishing represents a valuable alternative, and examples of receptor-based approaches, exploiting the large number of crystallographic protein structures determined to date, have been reported in the literature. To the best of our knowledge, no proper evaluation of such approaches is, however, reported yet. In the present work, we extensively assessed the reliability of docking-based target-fishing strategies. For this purpose, a set of X-ray structures belonging to different targets was selected, and a dataset of compounds, including 10 experimentally active ligands for each target, was created. A target-fishing benchmark database was then obtained, and used to assess the performance of 13 different docking procedures, in identifying the correct target of the dataset ligands. Moreover, a consensus docking-based target-fishing strategy was developed and evaluated. The analysis highlighted that specific features of the target proteins could affect the reliability of the protocol, which however, proved to represent a valuable tool in the proper applicability domain. Our study represents the first extensive performance assessment of docking-based target-fishing approaches, paving the way for the development of novel efficient receptor-based target fishing strategies.
dc.format.extent1023-1023
dc.language.isoen
dc.relation.haspartInternational Journal of Molecular Sciences
dc.relation.isreferencedbyMDPI AG
dc.rightsCC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjecttarget fishing
dc.subjectdocking
dc.subjectreverse screening
dc.subjectconsensus docking
dc.titleExtensive reliability evaluation of docking-based target-fishing strategies
dc.typeArticle
dc.type.genreJournal Article
dc.relation.doi10.3390/ijms20051023
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.creator.orcidGiordano, Antonio|0000-0002-5959-016X
dc.date.updated2020-12-16T18:00:43Z
refterms.dateFOA2020-12-16T18:00:48Z


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