Conformational properties of an artificial GM1 glycan cluster based on a metal-ligand complex

An artificial glycan cluster, in which 24 monosialotetrahexosylganglioside (GM1) glycans are transplanted to the interface of a metal-ligand complex, was recently proposed to investigate the interaction between GM1 glycan clusters and amyloidogenic proteins by NMR analysis. In this study, all-atom molecular dynamics simulations were performed to characterize the conformational properties of the artificial GM1 glycan cluster. We found that more than 65% of GM1 glycans are clustered by interchain hydrogen bonds. Interchain hydrogen bonds are mainly formed between Neu5Ac and Gal'. Pentamers were most frequently observed in the metal-ligand complex. GM1 glycans are tilted and hydrophobically interact with ligand moieties. The hydrophobic surface of the metal-ligand complex increases intrachain hydrogen bonds in each conformation of the GM1 glycans. The increase of intrachain hydrogen bonds stabilizes the local minimum conformations of the GM1 glycan in comparison with the monomeric one. Interchain hydrogen bonding between glycans and glycan-ligand hydrophobic interactions also contribute to this conformational stabilization. Our results provide the physicochemical properties of the new artificial GM1 glycan cluster under the thermal fluctuations for understanding its protein recognition and designing the drug material for amyloidogenic proteins.