Conformational Analysis of Oligoarabinofuranosides: Overcoming Torsional Barriers with Umbrella Sampling.

Abstract

In this report, the conformations of a series of mono- and oligoarabinofuranosides were probed through the use of umbrella sampling simulations with the AMBER force field and the GLYCAM carbohydrate parameter set. The rotamer population distribution about the exocyclic C4-C5 bonds and the puckering distributions of the rings obtained from these umbrella sampling simulations were found to be in excellent agreement with those obtained from conventional long MD simulations for small monosaccharide fragments. For larger systems, the conventional MD approach becomes impractical, and we propose the use of umbrella sampling to circumvent poor sampling of certain conformations. The same umbrella sampling simulations were used to calculate the distributions about the vicinal protons and ensemble-averaged vicinal proton-proton coupling constants ((3)JH,H). The distributions about the vicinal protons of a monomer, methyl-α-l-arabinofuranoside (1), were found to be very similar to those obtained from direct umbrella sampling simulations about the vicinal protons. We calculated (3)JH,H based on DFT-based Karplus-like relationships for l-arabinofuranosides. The (3)JH,H values were found to be very similar to those obtained with the conventional MD simulations. For 1, the (3)JH,H values obtained with the DFT-based Karplus equations agree very well with experimental results; the agreement is, however, not as good for the larger oligomers. An approach to determine the experimental rotamer populations from the simulations is also discussed.