Water irradiation devoid pulses enhance the sensitivity of 1H,1H nuclear Overhauser effects

V. S. Manu, Cristina Olivieri, Gianluigi Veglia

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The nuclear Overhauser effect (NOE) is one of NMR spectroscopy's most important and versatile parameters. NOE is routinely utilized to determine the structures of medium-to-large size biomolecules and characterize protein–protein, protein–RNA, protein–DNA, and protein–ligand interactions in aqueous solutions. Typical [1H,1H] NOESY pulse sequences incorporate water suppression schemes to reduce the water signal that dominates 1H-detected spectra and minimize NOE intensity losses due to unwanted polarization exchange between water and labile protons. However, at high- and ultra-high magnetic fields, the excitation of the water signal during the execution of the NOESY pulse sequences may cause significant attenuation of NOE cross-peak intensities. Using an evolutionary algorithm coupled with artificial intelligence, we recently designed high-fidelity pulses [Water irrAdiation DEvoid (WADE) pulses] that elude water excitation and irradiate broader bandwidths relative to commonly used pulses. Here, we demonstrate that WADE pulses, implemented into the 2D [1H,1H] NOESY experiments, increase the intensity of the NOE cross-peaks for labile and, to a lesser extent, non-exchangeable protons. We applied the new 2D [1H,1H] WADE-NOESY pulse sequence to two well-folded, medium-size proteins, i.e., the K48C mutant of ubiquitin and the Raf kinase inhibitor protein. We observed a net increase of the NOE intensities varying from 30 to 170% compared to the commonly used NOESY experiments. The new WADE pulses can be easily engineered into 2D and 3D homo- and hetero-nuclear NOESY pulse sequences to boost their sensitivity.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalJournal of biomolecular NMR
Volume77
Issue number1-2
DOIs
StatePublished - Apr 2023

Bibliographical note

Funding Information:
This work was supported by the National Institute of Health (HL 144130) to G.V. and a subcontract to GV from GM121735 (Marsha Rosner, P.I.).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature B.V.

Keywords

  • Artificial intelligence
  • Evolutionary algorithm
  • GENETICS-AI
  • Nuclear Overhauser effect
  • Pulse design
  • WADE pulses
  • [H,H] NOESY

PubMed: MeSH publication types

  • Journal Article

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