Ghose - Protein NMR: Methods and Protocols

Springer Science+Business Media LLC 2018

Caitlin M. Quinn 1, 2, Mingzhang Wang 1, 2 and Tatyana Polenova 1, 2

Abstract

As a result of profound gains in sensitivity and resolution afforded by ultrahigh magnetic fields, transformative applications in the fields of structural biology and materials science are being realized. The development of dual low temperature superconducting (LTS)/high-temperature superconducting (HTS) magnets has enabled the achievement of magnetic fields above 1 GHz (23.5 T), which will open doors to an unprecedented new range of applications. In this contribution, we discuss the promise of ultrahigh field magnetic resonance. We highlight several methodological developments pertinent at high-magnetic fields including measurement of 1H-1H distances and 1H chemical shift anisotropy in the solid state as well as studies of quadrupolar nuclei such as 17O. Higher magnetic fields have advanced heteronuclear detection in solution NMR, valuable for applications including metabolomics and disordered proteins, as well as expanded use of proton detection in the solid state in conjunction with ultrafast magic angle spinning. We also present several recent applications to structural studies of the AP205 bacteriophage, the M2 channel from Influenza A, and biomaterials such as human bone. Gains in sensitivity and resolution from increased field strengths will enable advanced applications of NMR spectroscopy including in vivo studies of whole cells and intact virions.

Key words

In the past two decades, the field of magnetic resonance has realized astounding advancements. One critical achievement toward progress in the fields of structural biology, materials science, and clinical imaging (to name just a few) has been the development of higher magnetic field strengths []. Higher magnetic fields yield profound improvements in both sensitivity and resolution.

The greatest drawback of nuclear magnetic resonance (NMR) relative to other analytical methods is relatively low sensitivity. Increasing magnetic field strength is a compelling way to increase sensitivity, as the signal-to-noise ratio (SNR, i.e., sensitivity) scales approximately as the power of 3/2 with the magnetic field strength [].

Increased magnetic fields also yield improvements in resolution:

where is the linewidth. As with improvements in sensitivity, increased resolution allows for the study of more complex systems and visualization of finer structural details.

Beyond significant gains in sensitivity and resolution, increased magnetic field strengths are particularly powerful for the study of quadrupolar nuclei ( I > ). Quadrupolar nuclei yield very broad spectra (on the order of MHz) due to the strong coupling (expressed by the coupling constant, C Q) between the nuclear quadrupolar moment and the electric field gradient (EFG). At higher magnetic field strengths, the contributions of the second-order quadrupolar interaction are reduced, leading to narrower spectra [].

Both NMR and clinical magnetic resonance imaging (MRI) benefit from increased magnetic field strengths. (For reviews of applications of high-magnetic fields to MRI, see refs..) Here, we focus on advancements in technology and methodology as applied in the burgeoning field of NMR at field strengths above 1 GHz. We also discuss several recent applications of high-magnetic fields to the study of biological systems.