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NMRmix: A Tool for the Optimization of Compound Mixtures in 1D (1)H NMR Ligand Affinity Screens
[Image: see text] NMR ligand affinity screening is a powerful technique that is routinely used in drug discovery or functional genomics to directly detect protein–ligand binding events. Binding events can be identified by monitoring differences in the 1D (1)H NMR spectrum of a compound with and with...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820789/ https://www.ncbi.nlm.nih.gov/pubmed/26965640 http://dx.doi.org/10.1021/acs.jproteome.6b00121 |
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author | Stark, Jaime L. Eghbalnia, Hamid R. Lee, Woonghee Westler, William M. Markley, John L. |
author_facet | Stark, Jaime L. Eghbalnia, Hamid R. Lee, Woonghee Westler, William M. Markley, John L. |
author_sort | Stark, Jaime L. |
collection | PubMed |
description | [Image: see text] NMR ligand affinity screening is a powerful technique that is routinely used in drug discovery or functional genomics to directly detect protein–ligand binding events. Binding events can be identified by monitoring differences in the 1D (1)H NMR spectrum of a compound with and without protein. Although a single NMR spectrum can be collected within a short period (2—10 min per sample), one-by-one screening of a protein against a library of hundreds or thousands of compounds requires a large amount of spectrometer time and a large quantity of protein. Therefore, compounds are usually evaluated in mixtures ranging in size from 3 to 20 compounds to improve the efficiency of these screens in both time and material. Ideally, the NMR signals from individual compounds in the mixture should not overlap so that spectral changes can be associated with a particular compound. We have developed a software tool, NMRmix, to assist in creating ideal mixtures from a large panel of compounds with known chemical shifts. Input to NMRmix consists of an (1)H NMR peak list for each compound, a user-defined overlap threshold, and additional user-defined parameters if default settings are not used. NMRmix utilizes a simulated annealing algorithm to optimize the composition of the mixtures to minimize spectral peak overlaps so that each compound in the mixture is represented by a maximum number of nonoverlapping chemical shifts. A built-in graphical user interface simplifies data import and visual evaluation of the results. |
format | Online Article Text |
id | pubmed-4820789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-48207892016-04-06 NMRmix: A Tool for the Optimization of Compound Mixtures in 1D (1)H NMR Ligand Affinity Screens Stark, Jaime L. Eghbalnia, Hamid R. Lee, Woonghee Westler, William M. Markley, John L. J Proteome Res [Image: see text] NMR ligand affinity screening is a powerful technique that is routinely used in drug discovery or functional genomics to directly detect protein–ligand binding events. Binding events can be identified by monitoring differences in the 1D (1)H NMR spectrum of a compound with and without protein. Although a single NMR spectrum can be collected within a short period (2—10 min per sample), one-by-one screening of a protein against a library of hundreds or thousands of compounds requires a large amount of spectrometer time and a large quantity of protein. Therefore, compounds are usually evaluated in mixtures ranging in size from 3 to 20 compounds to improve the efficiency of these screens in both time and material. Ideally, the NMR signals from individual compounds in the mixture should not overlap so that spectral changes can be associated with a particular compound. We have developed a software tool, NMRmix, to assist in creating ideal mixtures from a large panel of compounds with known chemical shifts. Input to NMRmix consists of an (1)H NMR peak list for each compound, a user-defined overlap threshold, and additional user-defined parameters if default settings are not used. NMRmix utilizes a simulated annealing algorithm to optimize the composition of the mixtures to minimize spectral peak overlaps so that each compound in the mixture is represented by a maximum number of nonoverlapping chemical shifts. A built-in graphical user interface simplifies data import and visual evaluation of the results. American Chemical Society 2016-03-11 2016-04-01 /pmc/articles/PMC4820789/ /pubmed/26965640 http://dx.doi.org/10.1021/acs.jproteome.6b00121 Text en Copyright © 2016 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Stark, Jaime L. Eghbalnia, Hamid R. Lee, Woonghee Westler, William M. Markley, John L. NMRmix: A Tool for the Optimization of Compound Mixtures in 1D (1)H NMR Ligand Affinity Screens |
title | NMRmix: A Tool
for the Optimization of Compound Mixtures
in 1D (1)H NMR Ligand Affinity Screens |
title_full | NMRmix: A Tool
for the Optimization of Compound Mixtures
in 1D (1)H NMR Ligand Affinity Screens |
title_fullStr | NMRmix: A Tool
for the Optimization of Compound Mixtures
in 1D (1)H NMR Ligand Affinity Screens |
title_full_unstemmed | NMRmix: A Tool
for the Optimization of Compound Mixtures
in 1D (1)H NMR Ligand Affinity Screens |
title_short | NMRmix: A Tool
for the Optimization of Compound Mixtures
in 1D (1)H NMR Ligand Affinity Screens |
title_sort | nmrmix: a tool
for the optimization of compound mixtures
in 1d (1)h nmr ligand affinity screens |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820789/ https://www.ncbi.nlm.nih.gov/pubmed/26965640 http://dx.doi.org/10.1021/acs.jproteome.6b00121 |
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