| Furanosides are important constituents of a number of glycoconjugates from many microorganisms. In particular, arabino- and galactofuranosides make up a major component of the complex cell wall structure of Mycobacterium tuberculosis, the organism responsible for tuberculosis. The highly flexible nature of these furanosyl moieties is believed to contribute significantly to their role in biological processes. Therefore, an understanding of their conformational preferences is an important area of research.;Access to these J values obtained from the conformational ensemble generated by the MD simulations of these molecules allowed for direct comparison to ring 3JH,H values obtained from NMR spectroscopy. Such an approach provides an alternative method to the PSEUROT approach and circumvents possible sources of error inherent within it.;The conformational determination of these ring systems is difficult due to their great flexibility, as they can adopt various envelope and twist conformations that are separated by low energy barriers. An important tool in the assessment of the solution conformations of these furanose ring systems has been a computer program named PSEUROT. It makes use of a generalized Karplus relationship, fits vicinal coupling constant data from NMR spectroscopy to the exocyclic dihedral angles between the coupled protons, and determines the relative populations of each conformer. However, this approach is not without its problems, as chemically unrealistic conformations are sometimes generated. In this dissertation, we make use of an alternative method as a tool to predict 3J H,H values, which can be used for direct comparison to those obtained experimentally. These studies are performed on a number of mycobacterial arabinofuranosides containing both alpha- and beta-linked residues. Density functional theory (DFT) calculations were carried out to derive Karplus relationships that are specifically tailored for these arabinofuranose ring systems. In addition, molecular dynamics simulations were performed on the alpha-Araf systems using a modified GLYCAM/AMBER approach and on beta-Ara f using a variety of force field approaches. The results from the various simulations are discussed, and an analysis of the resulting 3JH,H values is done. |
