Conformational Studies of Methyl β-d-Arabinofuranoside Using the AMBER/GLYCAM Approach.

Abstract

Furanosides are important constituents of a number of glycoconjugates from many microorganisms. The highly flexible nature of these furanosyl moieties is believed to contribute significantly to their role in biological processes. Therefore, an understanding of the conformational preferences of these molecules is an important area of research. As part of a larger program involved in the conformational analysis of mycobacterial oligofuranosides, molecular dynamics simulations on methyl β-d-arabinofuranoside (3) have been carried out using the AMBER forcefield and the GLYCAM carbohydrate parameter set. This approach was used to predict the rotamer population distribution about the hydroxymethyl group (C4-C5 bond) as well as the ring puckering of this flexible ring system. Comparison of the conformer distributions obtained during the simulation of 3 using the TIP3P water model with those obtained by analysis of (1)H-(1)H coupling constant data indicated that this water model was insufficient to describe the solvation of this system. However, the use of the TIP4P and TIP5P models led to improved agreement with conformer populations obtained from NMR data.