MOLECULAR-DYNAMICS SIMULATIONS OF AN ALPHA-(2-]8)-LINKED SIALIC-ACID TETRAMER IN VACUUM AND SOLVENT

Molecular dynamics (MD) simulations of an alpha-(2 --> 8)-linked tetra mer of sialic acid (N-acetyl neuraminic acid) were carried out in vacu um and in solvent (water), spanning 4 ns and 530 ps respectively. Prot onated and deprotonated forms of the carboxylic acid groups of sialic acid were modeled in the vacuum-based simulations; only the deprotonat ed form was studied in the water-based simulations. Nuclear magnetic r esonance (NMR) coupling constants and nuclear Overhauser effect (NOE) enhancements were calculated from the MD trajectories for the middle l inkages of the tetramer and compared with experimental data for the po lymer. A good agreement was not obtained between the experimental NMR data for the polymer and the NMR data extracted from the calculations on the tetramer. The question of whether the lack of agreement between experiment and simulation was due to the limited sampling of states d uring the MD simulations was addressed by means of Poisson simulations ; these simulations indicated that it was unlikely that the disagreeme nt was due to a sampling problem. (C) 1997 Elsevier Science B.V.