Molecular dynamics simulation and NMR study of a blood group H trisaccharide

Molecular dynamics simulations in vacuum and solution have been carried out on 2'-alpha-L-fucosyl-lactitol, a model for blood group H in conjunction with two-dimensional nmr measurements on the same compound. Three independent starting conformations for the dynamics were chosen from low energy conformations obtained by a phi/psi grid search. Nine 5 ns vacuum simulations of the trisaccharide were performed, employing three different ways to treat electrostatic interactions for each starting conformation: distance-dependent dielectric with epsilon = r, constant dielectric with epsilon = 1, or constant dielectric with epsilon = 80. In vacuum, transitions of phi and psi for the alpha-L-Fuc-(1-->2)-beta-D-Gal element occur in a cooperative manner. The virtual distance obtained for H1 in fucose to H2 in galactose from nuclear Overhauser effect spectroscopy experiments agree with one of the conformations of the trisaccharide in one of the three 100 ps aqueous simulations (phi/psi ca. -100 degrees/150 degrees), indicating this may be a dominant solution conformation. The rms fluctuations of the phi- and psi-dihedral angles were approximately 10 degrees for a conformational state, both in the vacuum and the aqueous simulations. For the simulations in vacuum, the agreement with experimental NOE data is reasonable when a constant dielectric of 1 is used (major conformers having phi/psi ca. -100 degrees/150 degrees and -140 degrees/100 degrees), whereas the agreement was poor with a constant dielectric of 80. Translational diffusion coefficients calculated from the simulation of the oligosaccharides were 0.12-0.18 x 10(-5) cm2/s and from nmr measurements 0.27 x 10(-5) cm2/s.