Solid-state NMR of biological samples


Z. Tošner


Faculty of Science, Charles University in Prague, Hlavova 8, 12843 Prague 2, Czech Republic


Solid-state nuclear magnetic resonance (NMR) is an invaluable spectroscopic method undergoing rapid development during the past years. In the area of biological research, it focuses on determination of atomic-resolution structures for so-called insoluble proteins, including difficult cases such as membrane proteins, amyloid fibrils, and proteins in heterogenous environments. Through efficient exploitation of isotropic as well as anisotropic (i.e., orientation dependent) nuclear spin interactions, it is now possible to routinely obtain 2- and 3-dimensional solid-state NMR spectra which in many respects resemble those known from liquid-state protein NMR spectroscopy. Such achievements were possible thanks to both improved theoretical understanding and technological advances. The solid-state NMR methodology includes fast and ultra-fast spinning of samples oriented at the magic angle with respect to the static magnetic field (magic angle spinning, MAS), use of strong radio-frequency fields and sophisticated pulse schemes as well as advanced isotope labeling with NMR active nuclei. Using such tools enables to fine-tune the effects of nuclear spin interactions during the course of an experiment and extract relevant structural informations. Beside the necessary assignment of resonances, inter-atomic distance constraints (or even precise distances) can be extracted and used for structure determination. With an attempt of reaching higher sensitivity, improved efficiencies of magnetization transfers and better spectral resolution, hundreds of different pulse methods have been developed. A general trend is that the highest quality has been obtained using increasingly advanced NMR pulse sequence design principles, including high-order average Hamiltonian theory, numerical optimizations based on analytical models, and most recently using optimal control procedures. All methods have their strong and weak points and much more techniques are expected to appear in this lively area of research.

In order to demonstrate the great potential of the solid-state NMR approach to structural characterization of biological materials, selected examples from the field-leading groups will be presented and major challenges together with some emerging methods will be briefly discussed.



The author is grateful to the Ministry of Education, Youth, and Sports of the Czech Republic for support through the grant No. RP MSMT 14/63.