NMR of biomolecules

The present section gives a brief description of the methodologies currently used for addressing the issues of resolution, sensitivity, nuclear connectivity and data assessments in solid-state NMR of biomolecules. 

This review evidences how, since the first solid-state NMR experiment in 1966 [9], we have witnessed a steady growth of knowledge on solid-state NMR of biomolecules from the detection of NMR... 

Solid-state NMR of organic materials has been reviewed by Lemaitre et al The current state of development of this field, as well as the NMR techniques and enrichment protocols have been considered. The O parameters derived from solid-state NMR experiments are summarised and the structural sensitivity of the approach to effects such as hydrogen bonding has been highlighted. The prospects and challenges for solid-state O NMR of biomolecules have also been presented. 

I. Bertini, K.S. McGreevy, G. Parigi, NMR of Biomolecules Towards Mechanistic Systems Biology, Wdey-VCH, Weinheim, 2012. 

Alrieri AS, Miller KE and Byrd RA (1996) A comparison of water suppression techniques using pulsed field gradients for high-resolution NMR of biomolecules. Magnetic Resonance Review 17 27-82. 

Gueron M and Plateau P (1996) Water signal suppression in NMR of biomolecules. In Grant DM and Harris RK (eds). Encyclopedia of Nuclear Magnetic Resonance, pp 4931-4942. Chichester Wiley. 

J. R. Lewandowski and L. Emsley, Protein Dynamics in the Solid State, in NMR of Biomolecules Towards Mechanistic Systems Biology, ed. I. Bertini, K. S. McGreevy and G. Parigi, Wiley-Blackwell, Weinheim, Germany, 2012, p. 367. 

A number of 2D NMR techniques are available for a variety of purposes They are especially valuable when attempting to determine the structure of complicated natural products and the conformations of biomolecules... 

MAS has been applied to a highly viscous cubic phase of a lyotropic LC formed by 1-monooleolyl-rac-glycerol and water in order to obtain liquid-like and 13C spectra.330 Deuterium, sodium, and fluorine NMR spectroscopy have been applied to study the phase behaviour of several dilute lamellar systems formed by low concentrations of an ra-hexadecylpyridinium salt, a sodium salt (e.g., NaBr, NaCl, or sodium trifluoroacetate), 1-hexanol, and D20.331 The 2H, 19F, and 23Na splittings were used to monitor the phase equilibria. The last two studies are motivated by the search of new lyotropic LC for the alignment of biomolecules. 

Since the discovery of the nuclear Overhauser effect (NOE, see previous section) [4, 5] and scalar coupling constants [36, 37] decades ago, NMR-derived structure calculations of biomolecules largely depended on the measurement of these two parameters [38]. Recently it became possible to use cross-correlated relaxation (CCR) to directly measure angles between bond vectors [39] (see also Chapt 7). In addition, residual dipolar couplings of weakly aligned molecules were discovered to measure the orientation of bond vectors relative to the alignment tensor (see Sect 16.5). Measurement of cross-correlated relaxation was described experimentally earlier for homonuclear cases [40, 41] and is widely used in solid-state NMR [42 14]. 

The book is separated into five major sections One short section on general aspects of spectroscopy, molecular biology and data evaluation is followed by an introduction into the NMR of commonly encountered classes of biomolecules. Thereafter, recent developments in spectroscopic techniques are highlighted. The next section describes experiments and practical aspects useful for the characterization of protein-ligand interactions. The final section presents an account on strategies for drug development using NMR written by experts from pharmaceutical industry. 

Structural problems subject to an NMR analysis may be subdivided into two main classes. The solution of part of the problems necessitates a maximum of structural information, including the spectral parameters of all the nuclei of the investigated molecule. Typical representatives of this kind of problems are the conformational analysis of biomolecules or the elucidation of the unknown structure of an isolated natural product by NMR... 

Fig. 8. Partial alignment of biomolecules using field oriented ordering media such as discoidal bicelles allows direct measurement of residual dipolar interactions under solution NMR conditions.

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