Structural Aspects of the O-glycosylation Linkage in Glycopeptides via MD Simulations and Comparison with NMR Experiments |
| |
Authors: | Aysegül Turupcu Matthias Diem Assoc Prof Lorna J Smith Prof Dr Chris Oostenbrink |
| |
Institution: | 1. Department of Material Sciences and Process Engineering, Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences Vienna, Vienna, Austria;2. Department of Chemistry, University of Oxford, Oxford, U.K. |
| |
Abstract: | 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 conformation 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. |
| |
Keywords: | Glycosylation Molecular dynamics Glycopeptides NMR spectroscopy |
|
|