Study of the Conformational Variety of the Oligosaccharide Substrates of Neuraminidases from Pathogens using Molecular Modeling

Abstract

Analysis of the conformational variety of the oligosaccharide fragments of the human glycan receptors LSTa (α-D-Neu5Ac-(2-3)-β-D-Gal-(1-3)-β-D-GlcNAc-(1-3)-β-D-Gal(1-4)-D-Glc) and LSTc (α-D-Neu5Ac-(2-6)-β-D-Gal-(1-3)-β-D-GlcNAc-(1-3)-β-D-Gal(1-4)-D-Glc) in aqueous solution has been performed with the comprehensive use of molecular modeling and statistical data processing followed by determination of major and minor stabilized conformers and selection of relevant topologies. The sialic acid ring conformational free energy landscape for both pentasaccharides has been reconstructed and analyzed giving a specification of the most probable distorted ring conformations of the basic chair ¹C₄ structure. The obtained results are in a good agreement with experimental data generated by nuclear magnetic resonance spectroscopy and X-ray crystallography.