Molecular Dynamics Simulations of Lipid-Linked Oligosaccharide in Membrane Bilayers

Abstract

Lipid-linked oligosaccharides (LLO) are intermediates in glycosylation in prokaryotes and eukaryotes. An LLO is composed of a lipid molecule joined by diphosphate to a sugar chain. However, the structure, dynamics, and orientation (with respect to bilayers) of LLO within biological membranes have not been explored previously. Using the recent CHARMM carbohydrate and general force fields, we have constructed two types of LLO: one based on the lipid molecule dolichol (DOL), which is found ubiquitously in eukaryotes, and one based on undecaprenol (UND), which is found in bacteria. We have simulated each LLO type in four different pure bilayer types with different hydrophobic thicknesses and saturations: DLPC (dilauroylphosphatidylcholine), DMPC (dimyristoylphosphatidylcholine), DOPC (dioleoylphosphatidylcholine), and SAPC (stearoylarachidonylcholine). The simulation results of each system will be discussed in terms of density distribution of each component along the membrane normal, RMSD and RMSF of oligosaccharides, oligosaccharides’ conformations, DOL and UND conformations, orientations of oligosaccharides with respect to the bilayer normal, and interactions of oligosaccharide with the bilayer.