Conformations Correlation times

Due to the fact that cross-correlated relaxation depends linearly on the correlation time, it can be used to determine the conformation of ligands when bound to target molecules, provided that the off rate is fast enough to enable detection of the cross-correlated relaxation rate via the free ligand [33, 34]. The conditions under which such an experiment can be performed are similar to those found for transferred NOEs [35], and, for Kd values... 

At longer saturation times the STDs exhibit a rather complex dependence on a number of factors including free ligand conformation and correlation time, and protein direct and indirect effects (Scheme 2). As a result, the relative intensities in the STD spectrum can sometimes vary with the saturation time. 

There remains an interpretation of ta to be found, ta exhibits an activation energy of about 0.43 0.1 eV, about three times as high as the C-C torsional barrier of 0.13 eV. The discrepancy must reflect the influence of the interactions with the environment and therefore ta appears to correspond to relaxation times most likely involving several correlated jumps. The experimental activation energy is in the range of that for the NMR correlation time associated with correlated conformational jumps in bulk PIB [136] (0.46 eV) and one could tentatively relate ta to the mechanism underlying this process (see later). 

Miscellaneous bRC. - The bRC of R. sphaeroides contains one accessible cysteine at the H subunit (His H-156). Poluektov et al.m have bound a specific nitroxide spin label to this Cys and used temperature-dependent multifrequency (9 and 130 GHz) EPR to determine the motion of the protein. It was found that the restricted dynamics can be described as fast libration in a cone with a correlation time of >10 9 s. Several dynamically nonequivalent sites were observed that indicate conformational substates of local protein structure. 

Indeed, 13C spin-lattice relaxation times can also reflect conformational changes of a protein, i.e. helix to random coil transitions. This was demonstrated with models of polyamino acids [178-180], in which definite conformations can be generated, e.g. by addition of chemicals or by changes in temperature. Thus effective molecular correlation times tc determined from spin-lattice relaxation times and the NOE factors were 24-32 ns/rad for the a carbons of poly-(/f-benzyl L-glutamate) in the more rigid helical form and about 0.8 ms/rad for the more flexible random coil form [180],... 

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