Oligosaccharides conformational parameters

MM2 has been applied frequently in mono- and disaccharide conformational analyses, but has not been extensively employed in oligosaccharide conformational determinations. The goal of the MM2 energy minimizations is often to allow relaxation of the geometrical parameters, and to provide more accurate estimates of the relative energies, for conformations obtained from rigid-residue conformational searches. ... 

Carbohydrates and especially oligosaccharides represent a special category for NMR spectroscopists. The structural characterization of oligosaccharides by NMR spectroscopy has remained challenging because of the lack of experimental parameters and the intrinsic high mobility in solution. For instance, the conformation around the exocyclic glycosidic bonds cannot unambiguously be determined from measurement of interresidue 1H-1H NOE measurements. 

Conformational analysis of oligosaccharides in solution by NMR spectroscopy is based on the study of chemical shifts, n.O.e. s, and three-bond, proton-carbon coupling constants. Generally, the experimental NMR parameters P. . , (such as n.O.e. s or... 

NMR spectroscopy has developed during the last few years into a very powerful method to establish both the conformation of an oligosaccharide in solution and in the crystalline state. The solution conformation of a saccharide can be determined generally by the combination of 13C-NMR and H-NMR techniques. 2-d methods became available in the last few years and are prerequisites for the elucidation of the three dimensional structure of an oligosaccharide [7]. Both NOE measurements [21] as well as traditional determination of coupling constants and chemical shifts are important tools for the determination of preferred conformations. 2-dimensional methods have greatly improved the accessibility of these parameters from complex molecules. 

Additional parameters for conformational analysis of oligosaccharides were derived by Imberty et al. [78],... 

Inasmuch as NMR relaxation phenoma, such as NOEs, are inversely proportional to the sixth power of the interproton separations, it is equally inappropriate to attempt to compute NOEs from a linearly averaged conformation of the oligosaccharide. If a distribution of conformations exists, as from a molecular dynamics or Monte Garlo simulation, the relaxation matrices (r,y ) for each conformation should be computed and the NMR parameters derived from the average relaxation matrix. An alternative approach is to weight the individual conformations located from a thorough conformational... 

In 1993 Rutherford et al. suggested that the poor performance of the Homans parameter set may reflect weaknesses of the computational method. 131 Despite the seemingly logical combination of parameters employed by Homans, after several attempts to reproduce experimental NOE intensities, Rutherford et al. concluded that the parameters were unsuitable for application in unrestrained MD simulations of oligosaccharides. 31 Moreover, those authors noted that the poor agreement with experiment was independent of the presence or absence of the exo-anomeric torsional terms. These conclusions were based on comparatively long trajectories of up to 1 ns performed in vacuo on a model mannobioside, a-D-Man(l-3)a-D-Man-OMe (8). However, the possibility remains that the poor performance was related to the short durations of the solvated simulations. No MD simulations with Homans parameters have been reported that approach the nanosecond time scale in the presence of explicit solvation. Recent MD simulations with explicit solvation indicate that conformational equilibration may not be achieved before 50—100 ps and that accurate ensemble averages may not be reached before 500 ps. > 3... 

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