Molecular dynamics simulations of hybrid and complex type oligosaccharides

Abstract

Conformational preferences of hybrid (G1cNAc₁Man₅GIcNAc₂) and complex (GlcNAc₁Man₃GlcNAc₂; GIcNAc₂Man₃GIcNAc₂) type asparagine-linked oligosaccharides and the corresponding bisected oligosaccharides have been studied by molecular dynamics simulations for 2.5 ns. The fluctuations of the core Man- α 1,3-Man fragment are restricted to a region around (-30°,-30°) due to a 'face-to-face' arrangement of bisecting GIcNAc and the β l,2-GIcNAc on the 1,3-arm. However, conformations where such a 'face-to-face' arrangement is disrupted are also accessed occasionally. The orientation of the 1,6-arm is affected not only by changes in X, but also by changes in Φ and Ψ around the core Man-al,6-Man linkage. The conformation around the core Man-α 1,6-Man linkage is different in the hybrid and the two complex types suggesting that the preferred values of Φ, Ψ and Χ are affected by the addition or deletion of saccharides to the α 1,6-linked mannose. The conformational data are in agreement with the available experimental studies and also explain the branch specificity of galactosyltransferases.