MOLECULAR-DYNAMICS SIMULATION AND NMR-STUDY OF A BLOOD GROUP-H TRISACCHARIDE

Molecular dynamics simulations in vacuum and solution have been carrie d out on 2'-alpha-L-fucosyllactitol, a model for blood group H in conj unction with two-dimensional nmr measurements on the same compound. Th ree independent starting conformations for the dynamics were chosen fr om low energy conformations obtained by a phi/psi grid search. Nine 5 ns vacuum simulations of the trisaccharide were performed, employing t hree different ways to treat electrostatic interactions for each start ing conformation: distance-dependent dielectric with epsilon = r, cons tant 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 dist ance obtained for H1 in fucose to H2 in galactose from nuclear Overhau ser effect spectroscopy experiments agree with one of the conformation s of the trisaccharide in one of the three 100 ps aqueous simulations (phi/psi ca. -100 degrees /150 degrees), indicating this may be a domi nant solution conformation. The rms fluctuations of the phi- and psi-d ihedral angles were similar to 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 a greement was poor with a constant dielectric of 80. Translational diff usion coefficients calculated from the simulation of the oligosacchari des were 0.12-0.18 X 10(-5) cm(2)/s and from nmr measurements 0.27 X 1 0(-5) cm(2)/s. (C) John Wiley & Sons, Inc.