title: Deciphering the glycosylation code.
abstract: Asparagine-linked carbohydrates profoundly impact glycoprotein folding, stability, and structure. However, the "glycosylation code" that relates these effects to protein sequence remains unsolved. We report atomically detailed replica exchange molecular dynamics simulations in explicit solvent that systematically investigate the impact of glycosylation upon peptides with the central sequon Pro-Asn-Gly/Ala-Thr-Trp/Ala. These simulations suggest that the effects of glycosylation may be quite sensitive to steric crowding by the side chain immediately following the glycosylation site but less sensitive to stacking interactions with the aromatic Trp residue. In addition, we compare our simulated ensembles with the known structures for full length glycoproteins. These structures corroborate the simulations and also suggest a remarkable consistency between the intraprotein and protein-glycan interactions of natural glycoproteins. Moreover, our analysis highlights the significance of left-handed conformations for compact β-hairpins at glycosylation sites. In summary, these studies elucidate basic biophysical principles for the glycosylation code.
authors.affiliation: Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Ellis
authors.forename: William G
authors.initials: WG
authors.lastname: Noid
mesh_terms: D000595:Amino Acid Sequence; D001216:Asparagine / Q000737:chemistry; D019295:Computational Biology; D030562:Databases, Protein; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary
chemical_list: D006023:Glycoproteins; D010455:Peptides; D001216:Asparagine