Additional dipolar coupling

The wide structural application of dipolar couplings is demonstrated by its use to validate models built by sequence homology methods. Additionally, dipolar couplings have been shown to reduce the RMSD between these models and the target structure. One example is the work reported by Chou et al., in which the RMSD of sequence homology models of the protein calmodulin, built from the structure of recoverin and parvalbumin, is reduced using heteronuclear dipolar couplings [110]. 

Molecular modeling is an indispensable tool in the determination of macromolecular structures from NMR data and in the interpretation of the data. Thus, state-of-the-art molecular dynamics simulations can reproduce relaxation data well [9,96] and supply a model of the motion in atomic detail. Qualitative aspects of correlated backbone motions can be understood from NMR structure ensembles [63]. Additional data, in particular residual dipolar couplings, improve the precision and accuracy of NMR structures qualitatively [12]. 

In addition to sample rotation, a particular solid state NMR experiment is further characterized by the pulse sequence used. As in solution NMR, a multitude of such sequences exist for solids many exploit through-space dipolar couplings for either signal enhancement, spectral assignment, interauclear distance determination or full correlation of the spectra of different nuclei. The most commonly applied solid state NMR experiments are concerned with the measurement of spectra in which intensities relate to the numbers of spins in different environments and the resonance frequencies are dominated by isotropic chemical shifts, much like NMR spectra of solutions. Even so, there is considerable room for useful elaboration the observed signal may be obtained by direct excitation, cross polarization from other nuclei or other means, and irradiation may be applied during observation or in echo periods prior to... 

Conversion of dipolar coupling data into three-dimensional structures presents a major challenge for folded proteins and for not-folded proteins, an additional set of obstacles must be confronted (Ackerman and Shortle, 2002). Nevertheless, the correlation of dipolar couplings measured under two sets of conditions establishes that the structures are likely to be highly similar. 

The estimated correlation times for the loop domains of the order of 10 4 s are obtained for the suppressed peaks in the [l-13C]amino-acid-labelled bR, including Gly, Ala, and Leu residues as shown in Figure 24C. The loop dynamics can be also examined by measurements of the 13C-1H dipolar couplings by DIPSHIFT experiment in which fluctuations of the Co,-Cp vector result in additional motional averaging as order parameters, in addition to the rotation of Ala methyl groups which scales the dipolar... 

Finally, a series of papers have been published on the solid state NMR spectra of a number of analgesic drugs. Jagannathan recorded the solid state 13C NMR spectrum of acetaminophen in bulk and dosage forms [60], From the solution-phase NMR spectrum, assignments of the solid state NMR resonances could be made in addition to explanations for the doublet structure of some resonances (dipolar coupling). Spectra of the dosage product from two sources indicated... 

In addition to the chemical shift information, an NMR spectrum may also contain coupling information. The types of couplings frequently present in NMR experiments include scalar (J) couplings between high-abundance nuclei such as protons, dipolar couplings that are important for cross-relaxation processes and the determination of nuclear Over-hauser effect (NOE) (described later in this chapter), and quadrupolar coupling associated with quadrupolar nuclei (/> 1/2). 

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]. 

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