Conformation and Dynamics at a Flexible Glycosidic Linkage Revealed by NMR Spectroscopy and Molecular Dynamics Simulations: Analysis of β-l-Fucp-(1→6)-α-d-Glcp-OMe in Water Solution

The intrinsic flexibility of carbohydrates facilitates different 3D structures in response to altered environments. At glycosidic (1→6)-linkages, three torsion angles are variable, and herein the conformation and dynamics of β-L-Fucp-(1→6)-α-D-Glcp-OMe are investigated using a combination of NMR spectroscopy and molecular dynamics (MD) simulations. The disaccharide shows evidence of conformational averaging for the ψ and ω torsion angles, best explained by a four-state conformational distribution. Notably, there is a significant population of conformations having ψ = 85° (clinal) in addition to those having ψ = 180° (antiperiplanar). Moderate differences in (13)C R1 relaxation rates are found to be best explained by axially symmetric tumbling in combination with minor differences in librational motion for the two residues, whereas the isomerization motions are occurring too slowly to be contributing significantly to the observed relaxation rates. The MD simulation was found to give a reasonably good agreement with experiment, especially with respect to diffusive properties, among which the rotational anisotropy, D∥/D⊥, is found to be 2.35. The force field employed showed too narrow ω torsion angles in the gauche-trans and gauche-gauche states as well as overestimating the population of the gauche-trans conformer. This information can subsequently be used in directing parameter developments and emphasizes the need for refinement of force fields for (1→6)-linked carbohydrates.