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Two-Dimensional NMR Lineshape Analysis

NMR titration experiments are a rich source of structural, mechanistic, thermodynamic and kinetic information on biomolecular interactions, which can be extracted through the quantitative analysis of resonance lineshapes. However, applications of such analyses are frequently limited by peak overlap...

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Detalles Bibliográficos
Autores principales: Waudby, Christopher A., Ramos, Andres, Cabrita, Lisa D., Christodoulou, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843008/
https://www.ncbi.nlm.nih.gov/pubmed/27109776
http://dx.doi.org/10.1038/srep24826
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author Waudby, Christopher A.
Ramos, Andres
Cabrita, Lisa D.
Christodoulou, John
author_facet Waudby, Christopher A.
Ramos, Andres
Cabrita, Lisa D.
Christodoulou, John
author_sort Waudby, Christopher A.
collection PubMed
description NMR titration experiments are a rich source of structural, mechanistic, thermodynamic and kinetic information on biomolecular interactions, which can be extracted through the quantitative analysis of resonance lineshapes. However, applications of such analyses are frequently limited by peak overlap inherent to complex biomolecular systems. Moreover, systematic errors may arise due to the analysis of two-dimensional data using theoretical frameworks developed for one-dimensional experiments. Here we introduce a more accurate and convenient method for the analysis of such data, based on the direct quantum mechanical simulation and fitting of entire two-dimensional experiments, which we implement in a new software tool, TITAN (TITration ANalysis). We expect the approach, which we demonstrate for a variety of protein-protein and protein-ligand interactions, to be particularly useful in providing information on multi-step or multi-component interactions.
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spelling pubmed-48430082016-04-29 Two-Dimensional NMR Lineshape Analysis Waudby, Christopher A. Ramos, Andres Cabrita, Lisa D. Christodoulou, John Sci Rep Article NMR titration experiments are a rich source of structural, mechanistic, thermodynamic and kinetic information on biomolecular interactions, which can be extracted through the quantitative analysis of resonance lineshapes. However, applications of such analyses are frequently limited by peak overlap inherent to complex biomolecular systems. Moreover, systematic errors may arise due to the analysis of two-dimensional data using theoretical frameworks developed for one-dimensional experiments. Here we introduce a more accurate and convenient method for the analysis of such data, based on the direct quantum mechanical simulation and fitting of entire two-dimensional experiments, which we implement in a new software tool, TITAN (TITration ANalysis). We expect the approach, which we demonstrate for a variety of protein-protein and protein-ligand interactions, to be particularly useful in providing information on multi-step or multi-component interactions. Nature Publishing Group 2016-04-25 /pmc/articles/PMC4843008/ /pubmed/27109776 http://dx.doi.org/10.1038/srep24826 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Waudby, Christopher A.
Ramos, Andres
Cabrita, Lisa D.
Christodoulou, John
Two-Dimensional NMR Lineshape Analysis
title Two-Dimensional NMR Lineshape Analysis
title_full Two-Dimensional NMR Lineshape Analysis
title_fullStr Two-Dimensional NMR Lineshape Analysis
title_full_unstemmed Two-Dimensional NMR Lineshape Analysis
title_short Two-Dimensional NMR Lineshape Analysis
title_sort two-dimensional nmr lineshape analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843008/
https://www.ncbi.nlm.nih.gov/pubmed/27109776
http://dx.doi.org/10.1038/srep24826
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