Towards understanding the interaction between oligosaccharides and water molecules Original Research Article

Complex carbohydrates are implicated in many important biological processes, and have a strong interaction with water. This close interplay with molecular water through multiple hydroxyls may be an integral part of their emergent structure and dynamics, as selected during evolution. Using molecular dynamics simulations with explicit water the interactions at the linkages within a variety of oligosaccharides are investigated and contrasted, in order to establish correlations between linkage orientation, sugar epimerization, and water interaction. In particular, interactions at α linkages, and between mannose and glucose residues, that are common in oligosaccharides are considered. Sugars joined by α linkages at the 2-, 3-, and 6-position were found to interact via a combination of weak hydrogen-bonds and water-bridges, which is dependent on the epimerization state of the sugars. Due to their three-dimensional structure, they are also likely to interact with noncontiguous sugar residues in an oligosaccharide, which can lead to ordered structures through the exclusion of water. On the other hand, β linkages (to 3- and 4-position) maintain strong hydrogen-bonds, have a limited ability to be involved in water-bridges, and predominantly interact with the directly attached sugars. Therefore, sequences of α-linked sugars form compact, branched structures that have conformational flexibility, and β linkages form extended, relatively rigid structures, suitable for structural molecules, and at the termini of protein bound oligosaccharides. These results provide further tentative ties between chemical structure, water interactions, and the emergent form and function of specific sugars and linkages in oligosaccharides.