MOLECULAR-DYNAMICS STUDY OF IDURONATE RING CONFORMATION

Molecular dynamics (MD) simulations of the conformation of the iduronate ring in a methyl glycoside and as the central residue in a trisaccharide have been carried out. Separate simulations were carried out with initial C-1(4), S-2(0), and C-4(1) iduronate ring conformations. Simulations were followed by observing the time development of the Cremer-Pople ring puckering parameters theta,phi2. Starting with chair geometries gave trajectories showing only ring oscillations close to the initial geometry. Simulations were performed with a S-2(0) Starting geometry using explicit water and in vacuum with dielectric constants (epsilon) of 1 and 80, as well as with distance-dependent dielectric functions of 2r and 4r. In both the explicit water simulation and the vacuum (epsilon = 80) simulations, extensive pseudorotational motion was observed in which boat and twist-boat ring conformers interconvert. The overall range of psi2 variation in the trisaccharide was about half of that observed in the methyl glycoside. The Haasnoot procedure for calculating H-H coupling constants in saccharides was applied to structures obtained from MD trajectories. Using MD time averaged couplings along with experimental data allowed the relative fractions of chair and boat/twist-boat forms to be derived.