Backbone motion

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]. 

NMRrelaxation and diffusion experiments provide important insights into both the internal molecular dynamics and the overall hydrodynamic behavior of unfolded and partly folded states. Local variations in backbone dynamics are correlated with propensities for local compaction of the polypeptide chain that results in constriction of backbone motions (Eliezer et al., 1998, 2000). This can occur through formation of... 

Fig. 4. Spectral densities of backbone motions in the pH 4.1 apomyoglobin intermediate at three different frequencies. Reproduced from Eliezer et al. (2000). Biochemistry 39, 2894-2901, with permission from the American Chemical Society.

Further, the electron-transport properties of the polymer 7 were enhanced by extending the separation between the redox center and backbone from a single Os—amino linkage to one that extends over 17 bonds. The goal was to provide mobility of the redox center independently of backbone motion, which is necessarily restricted by cross-linking. The mobility of the redox center can be characterized by an apparent diffusion coefficient, Z app- According to the relation proposed by Blauch and Saveant ... 

The symbols have their usual meanings (] ). From measured values of NTj and ri on a poly (butene-1 sulfone) of degree of polymerization 700 the values of t (in nanosec.) shown in Table III are obtained. The discrepancy between the values of from NT and from ri, particularly marked for the side-chain motions, indicates the inadequacy of the single-Tg model. Nevertheless it is evident that the backbone motions are relatively rapid. (Comparison to polybutene-1 (jW) shows that SO2 groups retard the motion of the copolymer chains by a factor of about 50.) The question now becomes why are these rapid motions NMR-active but dielectrically inactive One possible type of motion which would account for this is shown in Fig. 9. Five backbone bonds and six main-chain atoms are involved, i.e. the sequence C-S-C-C-S-C, with concerted segmental transitions about two C-S bond, allowing interconversion... 

The insensitivity of the nmr spectra to large changes in temperature is also indicative that the frozen backbone motions responsible for the spectral complexity are not easily thermally activated. The presence of chemically different triads composed of 1,2 and 1,4 units, each with a particular chemical shift, could... 

It was soon realized that a distribution of exponential correlation times is required to characterize backbone motion for a successful Interpretation of both carbon-13 Ti and NOE values in many polymers (, lO). A correlation function corresponding to a distribution of exponential correlation times can be generated in two ways. First, a convenient mathematical form can serve as the basis for generating and adjusting a distribution of correlation times. Functions used earlier for the analysis of dielectric relaxation such as the Cole-Cole (U.) and Fuoss-Kirkwood (l2) descriptions can be applied to the interpretation of carbon-13 relaxation. Probably the most proficient of the mathematical form models is the log-X distribution introduced by Schaefer (lO). These models are able to account for carbon-13 Ti and NOE data although some authors have questioned the physical insight provided by the fitting parameters (], 13) ... 

The other class of motion only now being introduced into interpretive models is oscillatory motion. Anisotropic oscillatory motions of substituent groups have been considered by Chachaty (12) but not in conjunction with a lattice description of backbone motion. No attempt to develop a model based on oscillatory backbone rearrangements is known to these authors, and this avenue may be very important for the interpretation of concentrated solutions, rubbery or amorphous solids, and especially glassy polymers... 

A. Jones If the backbone motion Is very slow then hi er... 

Dr. Bovey mentioned polysulfones. I would expect Ti to have an extended molecular weight dependence because the backbone motions are relatively slow In this case. 

Two-dimensional heteronuclear ( H- N) nuclear magnetic relaxation studies indicate that the dihydrofolate reductase-folate complex exhibits a diverse range of backbone fluctuations on the time-scale of picoseconds to nanoseconds To assess whether these dynamical features influence Michaelis complex formation, Miller et al used mutagenesis and kinetic measurements to assess the role of a strictly conserved residue, namely Gly-121, which displays large-amplitude backbone motions on the nanosecond time scale. Deletion of Gly-121 dramatically reduces the hydride transfer rate by 550 times there is also a 20-times decrease in NADPH cofactor binding affinity and a 7-fold decrease for NADP+ relative to wild-type. Insertion mutations significantly decreased both... 

Systematic departures from the Zimm moduli are observed at high frequencies (93, 117). These deviations appear to stem from the expected inadequacies of spring-bead models when the driving frequency approaches the frequency of the primitive backbone motions. The effects are attributed to a local resistance to the articulations of the chain which are required to bring about configurational... 

Lysine 41 is not in contact with the phosphate or sulfate in the p, site. It is nicely constrained by the structure so that it cannot be in contact without a gross fluctuation (backbone motion) from the average structure derived in the X-ray analysis. Cyclization of 3 -CMP would require appreciable rotation around the C2 -C3 bond, around the C3 -03 bond, and around the 03 -P bond. The phosphorus must move approximately 2 A relative to the 02 -C2 -C3 -03 configuration, and if B and R, do not move then the P04 would move directly toward Lys 41 and potentially make contact. 

Poly(n-butyl acrylate). A study of the relaxation properties of PBA was initiated for several reasons. There are two backbone carbons with directly bonded protons thus the effect of the side chain on backbone motion might be determined. Also, the CH carbon should more directly reflect the distribution of correlation times necessary to begin analysis of alkyl sidechain motion. Finally, the lack of the additional chain-CH3 groups significantly loosens motional constraints in PBA. The effect of this on the overall dynamics of PBA was of interest. 

Polymer Backbone Motion. Alternate descriptions of molecular motion utilize an effectively non-exponential autocorrelation function to describe polymer dynamics. One formalism is the use of a log-/2 distribution of correlation times in place of a single correlation time(14). Such a description may simulate the various time scales for overall and internal motions in polymers. 

This result suggests, if it is assumed that a C-H heteronuclear dipolar relaxation mechanism is operative, that methyl protons dominate the relaxation behavior of these carbons over much of the temperature range studied despite the 1/r dependence of the mechanism. The shorter T] for the CH as compared to the CH2 then arises from the shorter C-H distances. Apparently, the contributions to spectral density in the MHz region of the frequency spectrum due to backbone motions is minor relative to the sidegroup motion. The T p data for the CH and CH2 carbons also give an indication of methyl group rotational frequencies. 

The Gi-values in Table 14.6 demonstrate that the backbone motions and the moieties attached directly to the backbone, contribute the most to the damping peak and that long side chains act as "diluants". 

Comment For polystyrene, a /J-like relaxation process was attributed to phenyl-ring flips, while the main chain does not participate, see Section 3.3. Hence, when the backbone motion of a selectively labeled compound is studied, polystyrene can be regarded as a type A glass former. 

For backbone motions to modulate Ms, they must have correlation times shorter than about 30 ns (for X-band EPR spectroscopy) low-frequency modes with microsecond or longer correlation times cannot be characterized by Ms. Correlation times in the microsecond regime... 

There is little eridoice that inertial terms are important in the conrideration of backbone motions. This facilitates analyris of the linear movement in terms of normal modes determined by the stifihess constants and the riscous drag. The corresponding polar response is a superposition of simple decays dominated by the lowest one or two modes. 

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