Solid-state NMR Spectroscopy and Dynamic Nuclear Polarization

Abstract

Solid-state nuclear magnetic resonance (NMR) has become an important player in integrated structural biology approaches, particularly benefiting from the high sensitivity of NMR observables for small structural changes or ligand binding, the simple sample preparation based on sedimentation and the absence of any molecular-weight-dependent resonance broadening. The development of ultra-high magnetic-field strengths (>28 T) and fast magic-angle spinning techniques (>100 kHz) allows the study of, for instance, large proteins and their complexes, supramolecular assemblies or membrane proteins embedded in lipids requiring only sub-milligram amounts of protein sample. The basic principles of biomolecular solid-state NMR, sample preparation schemes and signal enhancement tools using dynamic nuclear polarization are discussed herein. Some recent examples for solid-state NMR embedded in the toolbox of integrated structural biology are presented in this chapter, focusing on employing solid-state NMR in concert with cryo-electron microscopy, X-ray diffraction, solution-state NMR, electron paramagnetic resonance and molecular dynamics simulations. Information accessible from solid-state NMR, such as protein dynamics, protein–ligand interactions, secondary-structure information and distance restraints is summarized and the strengths of solid-state NMR in protein structure determination are highlighted.