Por favor, use este identificador para citar o enlazar este documento: https://hdl.handle.net/2445/124522
Título: Computer-aided design of fragment mixtures for NMR-based screening
Autor: Arroyo, Xavier
Goldflam, Michael
Feliz Rodenas, Miguel
Belda, Ignasi
Giralt Lledó, Ernest
Materia: Ressonància magnètica nuclear
Disseny assistit per ordinador
Nuclear magnetic resonance
Computer-aided design
Fecha de publicación: 13-mar-2013
Publicado por: Public Library of Science (PLoS)
Resumen: 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.
Nota: Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0058571
Es parte de: PLoS One, 2013, vol. 8, num. 3, p. e58571
URI: https://hdl.handle.net/2445/124522
Recurso relacionado: https://doi.org/10.1371/journal.pone.0058571
ISSN: 1932-6203
Aparece en las colecciones:Articles publicats en revistes (Química Inorgànica i Orgànica)

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