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Facilitated Assignment of Large Protein NMR Signals with Covariance Sequential Spectra Using Spectral Derivatives

[Image: see text] Nuclear magnetic resonance (NMR) studies of larger proteins are hampered by difficulties in assigning NMR resonances. Human intervention is typically required to identify NMR signals in 3D spectra, and subsequent procedures depend on the accuracy of this so-called peak picking. We...

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Autores principales: Harden, Bradley J., Nichols, Scott R., Frueh, Dominique P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183633/
https://www.ncbi.nlm.nih.gov/pubmed/25226241
http://dx.doi.org/10.1021/ja5058407
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author Harden, Bradley J.
Nichols, Scott R.
Frueh, Dominique P.
author_facet Harden, Bradley J.
Nichols, Scott R.
Frueh, Dominique P.
author_sort Harden, Bradley J.
collection PubMed
description [Image: see text] Nuclear magnetic resonance (NMR) studies of larger proteins are hampered by difficulties in assigning NMR resonances. Human intervention is typically required to identify NMR signals in 3D spectra, and subsequent procedures depend on the accuracy of this so-called peak picking. We present a method that provides sequential connectivities through correlation maps constructed with covariance NMR, bypassing the need for preliminary peak picking. We introduce two novel techniques to minimize false correlations and merge the information from all original 3D spectra. First, we take spectral derivatives prior to performing covariance to emphasize coincident peak maxima. Second, we multiply covariance maps calculated with different 3D spectra to destroy erroneous sequential correlations. The maps are easy to use and can readily be generated from conventional triple-resonance experiments. Advantages of the method are demonstrated on a 37 kDa nonribosomal peptide synthetase domain subject to spectral overlap.
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spelling pubmed-41836332015-09-16 Facilitated Assignment of Large Protein NMR Signals with Covariance Sequential Spectra Using Spectral Derivatives Harden, Bradley J. Nichols, Scott R. Frueh, Dominique P. J Am Chem Soc [Image: see text] Nuclear magnetic resonance (NMR) studies of larger proteins are hampered by difficulties in assigning NMR resonances. Human intervention is typically required to identify NMR signals in 3D spectra, and subsequent procedures depend on the accuracy of this so-called peak picking. We present a method that provides sequential connectivities through correlation maps constructed with covariance NMR, bypassing the need for preliminary peak picking. We introduce two novel techniques to minimize false correlations and merge the information from all original 3D spectra. First, we take spectral derivatives prior to performing covariance to emphasize coincident peak maxima. Second, we multiply covariance maps calculated with different 3D spectra to destroy erroneous sequential correlations. The maps are easy to use and can readily be generated from conventional triple-resonance experiments. Advantages of the method are demonstrated on a 37 kDa nonribosomal peptide synthetase domain subject to spectral overlap. American Chemical Society 2014-09-16 2014-09-24 /pmc/articles/PMC4183633/ /pubmed/25226241 http://dx.doi.org/10.1021/ja5058407 Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Harden, Bradley J.
Nichols, Scott R.
Frueh, Dominique P.
Facilitated Assignment of Large Protein NMR Signals with Covariance Sequential Spectra Using Spectral Derivatives
title Facilitated Assignment of Large Protein NMR Signals with Covariance Sequential Spectra Using Spectral Derivatives
title_full Facilitated Assignment of Large Protein NMR Signals with Covariance Sequential Spectra Using Spectral Derivatives
title_fullStr Facilitated Assignment of Large Protein NMR Signals with Covariance Sequential Spectra Using Spectral Derivatives
title_full_unstemmed Facilitated Assignment of Large Protein NMR Signals with Covariance Sequential Spectra Using Spectral Derivatives
title_short Facilitated Assignment of Large Protein NMR Signals with Covariance Sequential Spectra Using Spectral Derivatives
title_sort facilitated assignment of large protein nmr signals with covariance sequential spectra using spectral derivatives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183633/
https://www.ncbi.nlm.nih.gov/pubmed/25226241
http://dx.doi.org/10.1021/ja5058407
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