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 principales:	Xavier Arroyo, Michael Goldflam, Miguel Feliz, Ignasi Belda, Ernest Giralt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dd367d864b2247b794244585d68d30f4
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id	oai:doaj.org-article:dd367d864b2247b794244585d68d30f4
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spelling	oai:doaj.org-article:dd367d864b2247b794244585d68d30f42021-11-18T07:53:36ZComputer-aided design of fragment mixtures for NMR-based screening.1932-620310.1371/journal.pone.0058571https://doaj.org/article/dd367d864b2247b794244585d68d30f42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516512/?tool=EBIhttps://doaj.org/toc/1932-6203Fragment-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.Xavier ArroyoMichael GoldflamMiguel FelizIgnasi BeldaErnest GiraltPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58571 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xavier Arroyo Michael Goldflam Miguel Feliz Ignasi Belda Ernest Giralt Computer-aided design of fragment mixtures for NMR-based screening.
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.
format	article
author	Xavier Arroyo Michael Goldflam Miguel Feliz Ignasi Belda Ernest Giralt
author_facet	Xavier Arroyo Michael Goldflam Miguel Feliz Ignasi Belda Ernest Giralt
author_sort	Xavier Arroyo
title	Computer-aided design of fragment mixtures for NMR-based screening.
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.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/dd367d864b2247b794244585d68d30f4
work_keys_str_mv	AT xavierarroyo computeraideddesignoffragmentmixturesfornmrbasedscreening AT michaelgoldflam computeraideddesignoffragmentmixturesfornmrbasedscreening AT miguelfeliz computeraideddesignoffragmentmixturesfornmrbasedscreening AT ignasibelda computeraideddesignoffragmentmixturesfornmrbasedscreening AT ernestgiralt computeraideddesignoffragmentmixturesfornmrbasedscreening
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Computer-aided design of fragment mixtures for NMR-based screening.

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