Conformational averaging

Koumanov A, Karshikoff A, Friis EP, Borchert TV (2001) Conformational averaging in pK calculations Improvement and limitations in prediction of ionization properties of proteins. J Phys Chem B 105 9339-9344. 

For comparison, the calculated linear and 2D spectra using ft = 12.3 cm-1 and 6 = 52°, which correspond to an a-helical structure (see the contour plot Fig. 19) for the isotopomer Ala -Ala-Ala are shown in Figure 21. The observed spectra for Ala -Ala-Ala are strikingly different from the calculated spectra for a molecule in an a-helical conformation. We emphasize here an important point In contrast to the NMR results on oligo(Ala), in which averaging of different backbone conformations might be present because measurements are made on a time scale that is slow compared to that of conformational motions, these vibrational spectroscopy results are detected on a very fast time scale (Hamm et al, 1999 Woutersen and Hamm, 2000, 2001). This rules out conformational averaging. 

Fig. 2. Illustration of the definitions of conformational coordinate 7Zn, e.g., 7Zn = ri, r2,. .., rn. The conformational distribution s (7U1) is sampled for the single molecule in the absence of interactions with solvent by suitable simulation procedures using coordinates appropriate for those procedures. The normalization adopted in this development is/sf (7Zn) dn1Z = V, the volume of the system. Thus, the conformational average that corresponds to adding the second brackets in going from Eq. (4) to Eq. (3) is evaluated with the distribution function sf (7Zn) = V.

Since NMR data may reflect the conformational averaging resulting from a substantial flexibility of DNA/RNA fragments, the parameters of the ensemble of structures obtained by MD refinement and experimental NMR restraints can display internal inconsistency. James and coworkers developed a method to determine the family of structural conform-ers and their populations based on NMR data [83]. This approach applies multiple-copy refinement with floating weights, which better reflects the conformational dynamics of nucleic acids. 

The configuration integral and all conformational averages are then evaluated using... 

In addition, while it is difficult to extrapolate the data in Figure 14 to conditions in aqueous solution, it is nevertheless clear that the nature of conformational averaging, which affects the interpretation of NMR parameters, depends on ring configuration, and that a singular approach to NMR parameter interpretation cannot be applied to all furanose structures. 

This does not mean that minor conformers and/or motional averaging are unimportant. The presence of even small amounts of minor conformers or limited conformational averaging as is suggested by the lowest energy two state structural solution could significantly affect the observed cross relaxation rate. The inverse sixth power dependence of the cross relaxation rate on interproton distance serves to strongly weight contributions from conformers with short interproton distances. Therefore the presence of even small amounts of conformers with short interproton distances can exert a disproportionate amount of influence on the observed cross relaxation rate. 

The n.m.r. spectrum (220 MHz) of N-deuteriated [Pt(en)3] shows small chemical shift differences which were attributed to incomplete conformational averaging. The possibility that these differences may arise from inherent magnetic non-equivalence was excluded on the basis of observed differences in Pt—H coupling constants. Comparison of the aqueous spectrum of... 

Accordingly, this rotamer provides a positive rotatory contribution due to exciton coupling, although the amplitude of the exciton Cotton effect is smaller than that in the cyclic system, due to conformational averaging . 

Within the frame of a program on simulation of the Brownian motion of chain molecules, the conformational static and dynamic properties of a model of PE are studied. In the present paper the same properties are systematically derived by using the RIS theory. As expected, there Is good agreement for static properties such as conformational averages and chain dimensions, in addition the local mobility of the chain Is favorably compared by the aid of the two approaches. 

Ke, the intramolecular excimer equilibrium constant under conditions where the dynamics or rotational Isomeric transitions is suppressed, is examined on the basis of the theory of macrocyclization [Flory, P. J.-, Suter, U. W. Mutter, M. J. Am. Chem. Soc. 1976, 98, 5733, 5740,5745], The conformational averages of the required moments and polynomials are calculated using their exact matrix generation method. The calculations can rationalize the appearance of a maximum near m = 15 In the 1 1 M that have been reported for pyrene-(CH2lrn-pyrene. In order to achieve this agreement, It is Imperative that the theoretical analysis incorporate the probability of a proper angular correlation of the two pyrene ring systems when the separation of their centers Is 0.35 nm. 

To account for the effects of conformational and torsional changes, for example those caused by rotational isomers, one has to introduce the properly weighted conformationally averaged electron density ... 

Benzoxazepines 9 were shown by NMR spectroscopy to be in the thiolactam structure <2004JMT(668)157>. Oxazepinium and thiazepinium salts 29 (X = O, S) were fully characterized by NMR spectroscopy. The spectral resolution had a substantial temperature dependence, which can be associated with an improvement in conformational averaging (Figure 5) <2003MRC975>. 

---