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Two-dimensional NMR lineshape analysis of single, multiple, zero and double quantum correlation experiments

Waudby, CA; Ouvry, M; Davis, B; Christodoulou, J; (2020) Two-dimensional NMR lineshape analysis of single, multiple, zero and double quantum correlation experiments. Journal of Biomolecular NMR , 74 pp. 95-109. 10.1007/s10858-019-00297-7. Green open access

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Abstract

NMR spectroscopy provides a powerful approach for the characterisation of chemical exchange and molecular interactions by analysis of series of experiments acquired over the course of a titration measurement. The appearance of NMR resonances undergoing chemical exchange depends on the frequency difference relative to the rate of exchange, and in the case of one-dimensional experiments chemical exchange regimes are well established and well known. However, two-dimensional experiments present additional complexity, as at least one additional frequency difference must be considered. Here we provide a systematic classification of chemical exchange regimes in two-dimensional NMR spectra. We highlight important differences between exchange in HSQC and HMQC experiments, that on a practical level result in more severe exchange broadening in HMQC spectra, but show that complementary alternatives to the HMQC are available in the form of HZQC and HDQC experiments. We present the longitudinal relaxation optimised SOFAST-H(Z/D)QC experiment for the simultaneous acquisition of sensitivity-enhanced HZQC and HDQC spectra, and the longitudinal and transverse relaxation optimised BEST-ZQ-TROSY for analysis of large molecular weight systems. We describe the application of these experiments to the characterisation of the interaction between the Hsp90 N-terminal domain and a small molecule ligand, and show that the independent analysis of HSQC, HMQC, HZQC and HDQC experiments provides improved confidence in the fitted dissociation constant and dissociation rate. Joint analysis of such data may provide improved sensitivity to detect and analyse more complex multi-state interaction mechanisms such as induced fit or conformational selection.

Type: Article
Title: Two-dimensional NMR lineshape analysis of single, multiple, zero and double quantum correlation experiments
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s10858-019-00297-7
Publisher version: https://doi.org/10.1007/s10858-019-00297-7
Language: English
Additional information: © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Chemical exchange, Double-quantum, Lineshape analysis, Multiple-quantum, Titrations, Two-dimensional NMR, Zero-quantum
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10089260
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