Structural aspects of the O‐glycosylation linkage in glycopeptides via MD simulations and comparison with NMR experiments

Aysegül Turupcu, Matthias Diem, Lorna Smith, Chris Oostenbrink
2019 ChemPhysChem  
A powerful conformational searching and enhanced sampling simulation method, and unbiased molecular dynamics simulations have been used along with NMR spectroscopic observables to provide a detailed structural view of O-glycosylation. For four model systems, the force-field parameters can accurately predict experimental NMR observables (J couplings and NOE's). This enables us to derive conclusions based on the generated ensembles, in which O-glycosylation affects the peptide backbone
more » ... n by forcing it towards to an extended conformation. An exception is described for β-GalNAc-Thr where the α content is increased and stabilized via hydrogen bonding between the sugar and the peptide backbone, which was not observed in the rest of the studied systems. These observations might offer an explanation for the evolutionary preference of α-linked GalNAc glycosylation instead of a β link.
doi:10.1002/cphc.201900079 pmid:30920077 pmcid:PMC6563056 fatcat:ipryaaazlzaszavn4p4pkdaini