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

Abstract

The intrinsic flexibility of carbohydrates facilitates different three-dimensional 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 in13 C R 1 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,, 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 gauchetrans 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.

Conformational Properties of α- or β-(1→6)-Linked Oligosaccharides: Hamiltonian Replica Exchange MD Simulations and NMR Experiments

“…However, the effect on the determined effective distances under conditions similar to those used in this study has recently shown to be negligible. 102 …”

“…Good agreement was found for ω conformational sampling in comparison to NMR spectroscopy and X-ray crystallography results. 73,74 While the above studies have yielded insights into the conformational properties of several disaccharides, concerns with respect to force field accuracy, diversity in the systems, and insufficient sampling of conformational space 23,37,67,73−76 warrant further studies of these biologically interesting systems. 77 …”

A molecular dynamics study of the effect of glycosidic linkage type in the hemicellulose backbone on the molecular chain flexibility

“…NMR experiments were carried out at 300 K on a 600 MHz Bruker AVANCE III spectrometer equipped with an inverse detection probe. The proton-proton cross-relaxation rate for the H1-H2 pair in a-cellobiose was measured using 1D 1 H, 1 H-NOESY experiments (Stott et al, 1997), and that of H4-H1 0 employed a 1D 1 H, 1 H-STEP-NOESY experiment (Hu et al, 2004;Pendrill et al, 2013). In all cases, selective excitation was achieved by single or double PFGSE modules utilizing 50-msec r-SNOB-or i-SNOB-2-shaped pulses for the NOESY experiment, and 50-65-msec r-SNOB-shaped pulses for the STEP-NOESY experiment.…”

Structure assignment and H/D-exchange behavior of several glycosylated polyphenols

“…In those cases, Karplus-relations for the two different diastereotopic protons H6 pro-R and H6 pro-S and their coupling to C4 and H5 have been developed. [25][26][27][28][29][30] However, to the best of our knowledge, there do not seem to be any publications that propose a quantitative description of dihedral angles  and  (i.e. ') for 6-O-substituted sugars based on a Karplus-relation for coupling of H6-C4.…”