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

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 elds, the excitation of the water signal during the execution of the NOESY pulse sequences may cause signi cant attenuation of NOE cross-peak intensities. Using an evolutionary algorithm coupled with arti cial intelligence, we recently designed high-delity 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 (RKIP). 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.

Artificial Intelligence-Powered Pulse Sequences in Nuclear Magnetic Resonance and Magnetic Resonance Imaging: Historical Trends, Current Innovations and Perspectives

“…Most of the additional crosspeaks come from the H N -H N interactions which are invisible in standard NOESY due to fast exchange of these protons with water. The average intensity of the spectrum increased as well by a factor of about 54% (compared to ES-NOESY) [52].…”

Slice through the water—Exploring the fundamental challenge of water suppression for benchtop NMR systems

“…Among these sequences, water suppression schemes based on the binomial selective inversion scheme, such as the commonly used W5-WATERGATE, are generally considered the most effective water suppression schemes, but due to its relatively wide suppression bandwidth, this comes at the expense of other signals near the water resonance. 25,26,32,33 Therefore, to evaluate the bandwidth of water suppression of these binomial selective inversion sequences, a series of 1 H NMR spectra were acquired across different offset values surrounding the water signal for different binomial inversion schemes without Pre-SAT. In this study, the following sequences were investigated: (1) JRS10, (2) JRS8, (3) JRS6, (4) JRS4, and (5) W5-WATERGATE.…”

AI-designed RF pulses enable fast pulsing heteronuclear multiple quantum coherence NMR experiment at high and ultra-high magnetic fields

“…These issues are exacerbated at high-and ultra-high magnetic fields, where the chemical shift breadth of all active nuclei is significantly broader. To resolve these issues, we used GENETICS-AI, GENErator of TrIply Compensated RF pulSes via Artificial Intelligence, 12,13 to design novel band-selective pulses into the SOFAST-HMQC experiment. GENETICS-AI utilizes an evolutionary algorithm that continuously populates a library RF pulse shapes with different phase and amplitude profiles.…”

“…13 A typical input for GENETICS-AI includes (a) the target bandwidth, (b) RF amplitude, (c) level of inhomogeneity compensation, and (d) operational fidelity. 12 The canonical scheme of the HMQC 14 experiment requires a pulse sequence 901-D-1801-D-acquisition on the 1 H channel and a 901-t 1 -901decoupling 15 on the heteronucleus ( 15 N or 13 C). In the SOFAST-HMQC experiment, 3 the 1 H 901 and 1801 pulses are replaced by two band-selective shapes, PC9 16 and REBURP, respectively.…”

“…25 In recent years, optimal control theory and optimization algorithms have played a critical role in pulse design. 24 GENETICS-AI is emerging as a new versatile approach for designing high-fidelity RF shapes for inversion, refocusing, excitation for broadband, and selective operations for solution 12,26,27 and solid-state 28 NMR spectroscopy. The excitation and the inversion pulses presented here are only examples of tailored RF pulse shapes that need to be implemented to improve the sensitivity and resolution of NMR applications at ultra-high magnetic fields.…”