Molecular dynamics simulations of hybrid and complex type oligosaccharides

Conformational preferences of hybrid (GlcNAc1Man5GlcNAc2) and complex (GlcNAc1Man3GlcNAc2; GlcNAc2Man3GlcNAc2) 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-alpha 1,3-Man fragment are restricted to a region around (-30 degrees, -30 degrees) due to a 'face-to-face' arrangement of bisecting GlcNAc and the beta 1,2-GlcNAc 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 chi, but also by changes in phi and psi around the core Man-alpha 1,6-Man linkage. The conformation around the core Man-alpha 1,6-Man linkage is different in the hybrid and the two complex types suggesting that the preferred values of phi, psi, and chi are affected by the addition or deletion of saccharides to the alpha 1,6-linked mannose. The conformational data are in agreement with the available experimental studies and also explain the branch specificity of galactosyltransferases.