Nearest-neighbor NMR spectroscopy: categorizing spectral peaks by their adjacent nuclei
| Autor: | Abhinav Dubey, Wolfgang Bermel, Wan-Na Chen, Nikolaos G. Sgourakis, Meng Zhang, Paul Coote, Soumya P. Behera, Gerhard Wagner, Haribabu Arthanari, Viviane S. De Paula |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Magnetic Resonance Spectroscopy Streptococcus pyogenes Science General Physics and Astronomy 010402 general chemistry 01 natural sciences Methylation Quantum mechanics General Biochemistry Genetics and Molecular Biology Radio spectrum Maltose-Binding Proteins Article k-nearest neighbors algorithm 03 medical and health sciences Magnetization Humans Computer Simulation Amino Acids lcsh:Science Physics Quantitative Biology::Biomolecules Multidisciplinary Relaxation (NMR) Resonance Reproducibility of Results General Chemistry Nuclear magnetic resonance spectroscopy 0104 chemical sciences 030104 developmental biology Structural biology Orders of magnitude (time) lcsh:Q Biological system Solution-state NMR |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-7 (2020) |
| ISSN: | 2041-1723 |
| Popis: | Methyl-NMR enables atomic-resolution studies of structure and dynamics of large proteins in solution. However, resonance assignment remains challenging. The problem is to combine existing structural informational with sparse distance restraints and search for the most compatible assignment among the permutations. Prior classification of peaks as either from isoleucine, leucine, or valine reduces the search space by many orders of magnitude. However, this is hindered by overlapped leucine and valine frequencies. In contrast, the nearest-neighbor nuclei, coupled to the methyl carbons, resonate in distinct frequency bands. Here, we develop a framework to imprint additional information about passively coupled resonances onto the observed peaks. This depends on simultaneously orchestrating closely spaced bands of resonances along different magnetization trajectories, using principles from control theory. For methyl-NMR, the method is implemented as a modification to the standard fingerprint spectrum (the 2D-HMQC). The amino acid type is immediately apparent in the fingerprint spectrum. There is no additional relaxation loss or an increase in experimental time. The method is validated on biologically relevant proteins. The idea of generating new spectral information using passive, adjacent resonances is applicable to other contexts in NMR spectroscopy. The structure and dynamics of large proteins and complexes can be studied by methyl-NMR but resonance assignment is still challenging. Here, the authors present a NMR method that leverages optimal control pulse design to unambiguously distinguish between Leu and Val using a simple 2D HMQC experiment and they apply it to several proteins including Cas9, interleukin, and human translation initiation factor eIF4a. |
| Databáze: | OpenAIRE |
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