Molecular dynamics simulation and nuclear magnetic resonance studies of the terminal glucotriose unit found in the oligosaccharide of glycoprotein precursors.

The trisaccharide alpha-d-Glcp-(1 --> 2)-alpha-d-Glcp-(1 --> 3)-alpha-d-Glcp-OMe, a model for the terminal glucotriose in Glc(3)Man(9)GlcNAc(2) in glycoprotein precursors, has been investigated by computer simulations and NMR spectroscopy. Molecular dynamics simulations were performed for 1 ns in aqueous solution and 20 ns in vacuo using the CHARMM-based force fields PARM22 and CHEAT95. An additional Monte Carlo simulation with the HSEA force field was also carried out. Experimental NMR data in water solution was obtained from measurement of long-range (1)H,(13)C heteronuclear trans-glycosidic coupling constants, (3)J(H,C), using one-dimensional Hadamard spectroscopy. Calculation of the (3)J(H,C) values from the simulations showed a varying degree of agreement to experimental data. It could be shown from simulation that the φ torsion angles differed, which was corroborated by the NMR measurements. Analyses were done of radial distribution functions and of hydrogen bonds. It was suggested that intermolecular hydrogen bonds were present, but in contrast to simulation the results from NMR spectroscopy did not support any major contribution. Hence, their influence on the conformation of the trisaccharide is rather small. Comparison of (1)H NMR chemical shifts for the trisaccharide and the glucotriose in Glc(3)Man(8)GlcNAc revealed high similarity. However, the derived conformation of the model substance in this work differed at one glycosidic torsion angle compared to the glucotriose on a large oligosaccharide. Copyright 2000 Academic Press.