Residual dipolar coupling Resolution

Furrer, J., John, M., Kessler, H., Luy, B. /-Spectroscopy in the presence of residual dipolar couplings determination of one-bond coupling constants and scalable resolution. 

Since its first description in 1971 [35], gel-phase NMR was applied to peptide chemistry by Manatt and coworkers [36, 37], These authors used 13C NMR to determine the extent of chloromethylation of crosslinked polymers and 19F NMR to monitor protection-deprotection reactions. These two nuclei are the most commonly used in these types of studies, mainly because of their significant chemical shift dispersion, which can alleviate in part the resolution loss due to the non ideal linewidth obtained in the gel state. Apart from restricted molecular motion, that shortens T2 because of an efficient transverse relaxation, other sources of line-broadening derive from magnetic susceptibility variations within the sample (due to the physical heterogeneity of the system) and residual dipolar couplings. 

Cierpicki T, Liang B, Tamm LK, Bushweller JH. Increasing the accuracy of solution NMR structures of membrane proteins by application of residual dipolar couplings. High-resolution structure of outer membrane protein A. J. Am. Chem. Soc. 2006 128 6947-6951. 

While methods of spectrum analysis capable of super-resolution exist, that is, methods that can achieve resolution greater than l/Wx, the most common of these, linear prediction (LP) extrapolation, has substantial drawbacks. LP extrapolation is used to extrapolate signals beyond the measured interval. While this can dramatically suppress truncation artifacts associated with zero-filling as well as improve resolution, because LP extrapolation implicitly assumes exponential decay it can lead to subtle frequency bias when the signal decay is not perfectly exponential [8]. This bias can have detrimental consequences for applications that require the determination of small fi-equency differences, such as measurement of residual dipolar couplings (RDCs). 

Backbone scalar couplings are widely used in NMR studies of structure and dynamics of biomolecules [93]. Additionally, there is a substantial interest in precise determination of residual dipolar couplings for structural studies of weakly oriented biomolecules. Most of the relevant coupling constants in proteins are rather small - of the magnitude from a few to a hundred hertz. Therefore, in order to achieve the sufficient resolution in indirectly measured dimensions, the majority of traditional methods devoted to coupling constants determination in biomolecules are limited to two-dimensional techniques, which frequently suffer from peak overlap. However, the random sampling of evolution time domain allows one to obtain spectra of resolution limited only by transverse relaxation... 

Ishii Y, Markus MA et al (2001) Controlling residual dipolar couplings in high-resolution NMR of proteins by strain induced alignment in a gel. J Biomol NMR 21(2) 141-151... 

Nodet G et al (2009) Quantitative description of backbone conformational sampling of unfolded proteins at amino acid resolution from NMR residual dipolar couplings. J Am Chem Soc 131(49) 17908-17918... 

Today there are many variants of the basic sequences. The most important modifications are the transverse relaxation optimized experiments suitable for perdeut-erated proteins, the sensitivity enhanced versions and the constant time (CT) implementations for improved resolution. Furthermore there are many experiments based on the basic sequences designed to measure scalar and residual dipolar couplings, often also implemented with spin-state selection as exemplified in Fig. 14.54. 

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