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Solution State Methyl NMR Spectroscopy of Large Non-Deuterated Proteins Enabled by Deep Neural Networks
Open accessPreprint — published as 10.1038/s41467-024-49378-8 · Paper page
Abstract
Methyl-TROSY nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for characterising large biomolecules in solution. However, preparing samples for these experiments is arduous and entails deuteration, limiting its use. Here we demonstrate that NMR spectra recorded on protonated, uniformly 13 C labelled, samples can be processed using deep neural networks to yield spectra that are of similar quality to typical deuterated methyl-TROSY spectra, potentially providing more information at a fraction of the cost. We validated the new methodology experimentally on three proteins with molecular weights in the range 42-360 kDa and further by analysing deep learning-processed NOESY spectra of Escherichia coli Malate Synthase G (81 kDa), where observed NOE cross-peaks were in good agreement with the available structure. The new method represents a substantial advance in the field of using deep learning to analyse complex magnetic resonance data and could have a major impact on the study of large biomolecules in the years to come.
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Science in the age of large language models
Birhane, A., Kasirzadeh, A., Leslie, D., & Wachter, S. (2023) · Nature Reviews Physics · doi:10.1038/s42254-023-00581-4 · Cited by 344
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Metadata
- Authors
- Karunanithy, G., Shukla, V. K., & Hansen, D. F.
- Affiliations
- University College London (GB)
- Corresponding author
- Hansen, D. Flemming
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2023-09-17
- OpenAlex
- W4386811693
- Cited by
- 4
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Figshare (submittedVersion, cc-by)
- The Francis Crick Institute (cc-by)
- Zenodo (CERN European Organization for Nuclear Research) (cc-by)
- Funders
- Wellcome Trust (FC001029, 101569/Z/13/Z)
- Francis Crick Institute (FC001029)
- UK Research and Innovation (EP/X036782/1)
- Cancer Research UK (FC010233, FC001029)
- University College London
- University of Oxford
- National Institutes of Health
- Medical Research Council (FC001029)
- Engineering and Physical Sciences Research Council (EP/X036782/1, EP/R029849/1)
- Biotechnology and Biological Sciences Research Council (BB/R000255/1)
- National Institute of General Medical Sciences (P41GM111135)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Spectroscopy › Molecular spectroscopy and chirality
- Keywords
- deep neural network, large proteins, NOESY, spectral data processing, solution NMR
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