Unexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision

Abstract Rationalizing the identification of hidden similarities across the repertoire of druggable protein cavities remains a major hurdle to a true proteome-wide structure-based discovery of novel drug candidates. We recently described a new computational approach (ProCare), inspired by numerical...

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Autores principales:	Merveille Eguida, Didier Rognan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Binding sites Similarity Point cloud registration Information technology T58.5-58.64 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/3b6c0f8b42f341fbbf2ac7c15015ffe3
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spelling	oai:doaj.org-article:3b6c0f8b42f341fbbf2ac7c15015ffe32021-11-28T12:30:23ZUnexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision10.1186/s13321-021-00567-31758-2946https://doaj.org/article/3b6c0f8b42f341fbbf2ac7c15015ffe32021-11-01T00:00:00Zhttps://doi.org/10.1186/s13321-021-00567-3https://doaj.org/toc/1758-2946Abstract Rationalizing the identification of hidden similarities across the repertoire of druggable protein cavities remains a major hurdle to a true proteome-wide structure-based discovery of novel drug candidates. We recently described a new computational approach (ProCare), inspired by numerical image processing, to identify local similarities in fragment-based subpockets. During the validation of the method, we unexpectedly identified a possible similarity in the binding pockets of two unrelated targets, human tumor necrosis factor alpha (TNF-α) and HIV-1 reverse transcriptase (HIV-1 RT). Microscale thermophoresis experiments confirmed the ProCare prediction as two of the three tested and FDA-approved HIV-1 RT inhibitors indeed bind to soluble human TNF-α trimer. Interestingly, the herein disclosed similarity could be revealed neither by state-of-the-art binding sites comparison methods nor by ligand-based pairwise similarity searches, suggesting that the point cloud registration approach implemented in ProCare, is uniquely suited to identify local and unobvious similarities among totally unrelated targets.Merveille EguidaDidier RognanBMCarticleBinding sitesSimilarityPoint cloud registrationInformation technologyT58.5-58.64ChemistryQD1-999ENJournal of Cheminformatics, Vol 13, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Binding sites Similarity Point cloud registration Information technology T58.5-58.64 Chemistry QD1-999
spellingShingle	Binding sites Similarity Point cloud registration Information technology T58.5-58.64 Chemistry QD1-999 Merveille Eguida Didier Rognan Unexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision
description	Abstract Rationalizing the identification of hidden similarities across the repertoire of druggable protein cavities remains a major hurdle to a true proteome-wide structure-based discovery of novel drug candidates. We recently described a new computational approach (ProCare), inspired by numerical image processing, to identify local similarities in fragment-based subpockets. During the validation of the method, we unexpectedly identified a possible similarity in the binding pockets of two unrelated targets, human tumor necrosis factor alpha (TNF-α) and HIV-1 reverse transcriptase (HIV-1 RT). Microscale thermophoresis experiments confirmed the ProCare prediction as two of the three tested and FDA-approved HIV-1 RT inhibitors indeed bind to soluble human TNF-α trimer. Interestingly, the herein disclosed similarity could be revealed neither by state-of-the-art binding sites comparison methods nor by ligand-based pairwise similarity searches, suggesting that the point cloud registration approach implemented in ProCare, is uniquely suited to identify local and unobvious similarities among totally unrelated targets.
format	article
author	Merveille Eguida Didier Rognan
author_facet	Merveille Eguida Didier Rognan
author_sort	Merveille Eguida
title	Unexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision
title_short	Unexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision
title_full	Unexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision
title_fullStr	Unexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision
title_full_unstemmed	Unexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision
title_sort	unexpected similarity between hiv-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3b6c0f8b42f341fbbf2ac7c15015ffe3
work_keys_str_mv	AT merveilleeguida unexpectedsimilaritybetweenhiv1reversetranscriptaseandtumornecrosisfactorbindingsitesrevealedbycomputervision AT didierrognan unexpectedsimilaritybetweenhiv1reversetranscriptaseandtumornecrosisfactorbindingsitesrevealedbycomputervision
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Unexpected similarity between HIV-1 reverse transcriptase and tumor necrosis factor binding sites revealed by computer vision

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