Computer-aided design of fragment mixtures for NMR-based screening

Fragment-based drug discovery is widely applied both in industrial and in academic screening programs. Several screening techniques rely on NMR to detect binding of a fragment to a target. NMR-based methods are among the most sensitive techniques and have the further advantage of yielding a low rate...

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Autores: Arroyo, Xavier, Goldflam, Michael, Feliz Rodenas, Miguel, Belda, Ignasi, Giralt Lledó, Ernest
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/124522
Acesso em linha:https://hdl.handle.net/2445/124522
Access Level:acceso abierto
Palavra-chave:Ressonància magnètica nuclear
Disseny assistit per ordinador
Nuclear magnetic resonance
Computer-aided design
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spelling Computer-aided design of fragment mixtures for NMR-based screeningArroyo, XavierGoldflam, MichaelFeliz Rodenas, MiguelBelda, IgnasiGiralt Lledó, ErnestRessonància magnètica nuclearDisseny assistit per ordinadorNuclear magnetic resonanceComputer-aided designFragment-based drug discovery is widely applied both in industrial and in academic screening programs. Several screening techniques rely on NMR to detect binding of a fragment to a target. NMR-based methods are among the most sensitive techniques and have the further advantage of yielding a low rate of false positives and negatives. However, NMR is intrinsically slower than other screening techniques; thus, to increase throughput in NMR-based screening, researchers often assay mixtures of fragments, rather than single fragments. Herein we present a fast and straightforward computer-aided method to design mixtures of fragments taken from a library that have minimized NMR signal overlap. This approach enables direct identification of one or several active fragments without the need for deconvolution. Our approach entails encoding of NMR spectra into a computer-readable format that we call a fingerprint, and minimizing the global signal overlap through a Monte Carlo algorithm. The scoring function used favors a homogenous distribution of the global signal overlap. The method does not require additional experimental work: the only data required are NMR spectra, which are generally recorded for each compound as a quality control measure before its insertion into the library.Public Library of Science (PLoS)2018201820132018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion7 p.application/pdfhttps://hdl.handle.net/2445/124522Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0058571PLoS One, 2013, vol. 8, num. 3, p. e58571https://doi.org/10.1371/journal.pone.0058571cc-by (c) Arroyo, X. et al., 2013http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1245222026-05-29T05:05:01Z
dc.title.none.fl_str_mv Computer-aided design of fragment mixtures for NMR-based screening
title Computer-aided design of fragment mixtures for NMR-based screening
spellingShingle Computer-aided design of fragment mixtures for NMR-based screening
Arroyo, Xavier
Ressonància magnètica nuclear
Disseny assistit per ordinador
Nuclear magnetic resonance
Computer-aided design
title_short Computer-aided design of fragment mixtures for NMR-based screening
title_full Computer-aided design of fragment mixtures for NMR-based screening
title_fullStr Computer-aided design of fragment mixtures for NMR-based screening
title_full_unstemmed Computer-aided design of fragment mixtures for NMR-based screening
title_sort Computer-aided design of fragment mixtures for NMR-based screening
dc.creator.none.fl_str_mv Arroyo, Xavier
Goldflam, Michael
Feliz Rodenas, Miguel
Belda, Ignasi
Giralt Lledó, Ernest
author Arroyo, Xavier
author_facet Arroyo, Xavier
Goldflam, Michael
Feliz Rodenas, Miguel
Belda, Ignasi
Giralt Lledó, Ernest
author_role author
author2 Goldflam, Michael
Feliz Rodenas, Miguel
Belda, Ignasi
Giralt Lledó, Ernest
author2_role author
author
author
author
dc.subject.none.fl_str_mv Ressonància magnètica nuclear
Disseny assistit per ordinador
Nuclear magnetic resonance
Computer-aided design
topic Ressonància magnètica nuclear
Disseny assistit per ordinador
Nuclear magnetic resonance
Computer-aided design
description Fragment-based drug discovery is widely applied both in industrial and in academic screening programs. Several screening techniques rely on NMR to detect binding of a fragment to a target. NMR-based methods are among the most sensitive techniques and have the further advantage of yielding a low rate of false positives and negatives. However, NMR is intrinsically slower than other screening techniques; thus, to increase throughput in NMR-based screening, researchers often assay mixtures of fragments, rather than single fragments. Herein we present a fast and straightforward computer-aided method to design mixtures of fragments taken from a library that have minimized NMR signal overlap. This approach enables direct identification of one or several active fragments without the need for deconvolution. Our approach entails encoding of NMR spectra into a computer-readable format that we call a fingerprint, and minimizing the global signal overlap through a Monte Carlo algorithm. The scoring function used favors a homogenous distribution of the global signal overlap. The method does not require additional experimental work: the only data required are NMR spectra, which are generally recorded for each compound as a quality control measure before its insertion into the library.
publishDate 2013
dc.date.none.fl_str_mv 2013
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/124522
url https://hdl.handle.net/2445/124522
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0058571
PLoS One, 2013, vol. 8, num. 3, p. e58571
https://doi.org/10.1371/journal.pone.0058571
dc.rights.none.fl_str_mv cc-by (c) Arroyo, X. et al., 2013
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Arroyo, X. et al., 2013
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 7 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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