Ramachandran‐type plots for glycosidic linkages: Examples from molecular dynamic simulations using the Glycam06 force field

Abstract

The goals of this article are to (1) provide further validation of the Glycam06 force field, specifically for its use in implicit solvent molecular dynamic (MD) simulations, and (2) to present the extension of G.N. Ramachandran's idea of plotting amino acid phi and psi angles to the glycosidic phi, psi, and omega angles formed between carbohydrates. As in traditional Ramachandran plots, these carbohydrate Ramachandran-type (carb-Rama) plots reveal the coupling between the glycosidic angles by displaying the allowed and disallowed conformational space. Considering two-bond glycosidic linkages, there are 18 possible conformational regions that can be defined by (alpha, phi, psi) and (beta, phi, psi), whereas for three-bond linkages, there are 54 possible regions that can be defined by (alpha, phi, psi, omega) and (beta, phi, psi, omega). Illustrating these ideas are molecular dynamic simulations on an implicitly hydrated oligosaccharide (700 ns) and its eight constituent disaccharides (50 ns/disaccharide). For each linkage, we compare and contrast the oligosaccharide and respective disaccharide carb-Rama plots, validate the simulations and the Glycam06 force field through comparison to experimental data, and discuss the general trends observed in the plots.

Shaping up for structural glycomics: a predictive protocol for oligosaccharide conformational analysis applied to N-linked glycans

“…However, on the α(1→3) branch only, this bond transitions after 9 μs in the simulation to state XVIII , which persists for ≈0.5 μs. The predicted relative populations of these conformers accord with the X-ray data, which have not been the case in prior ns-simulations (e.g., XVIII has been reported previously at <1% in the disaccharide 30 ). …”

Immunoglobulin G1 Fc Domain Motions: Implications for Fc Engineering

“…That the α1-6Man branch of a biantennary N-glycan experiences greater conformational heterogeneity than the α1-3Man branch of the glycan is expected based on the presence of an additional glycosidic torsion angle (ω) 32 . Thus, if restricting the Fc N-glycan is necessary for effective FcγRIIIa binding, a conformationally-constraining interaction between the Fc polypeptide and its glycan through the α1-6Man-linked branch is poised to provide the greatest total glycan restriction with the smallest possible interface.…”

Molecular-Level Simulation of Pandemic Influenza Glycoproteins

“…Curiously, glycosylation at the 150-loop site has been shown to play a role in neurovirulence in mice (50). To the best of our knowledge, there have been no atomic-level computational investigations to date that include bound sialoglycans on NA, yet, the development of an improved generalizable carbohydrate force field, GLYCAM06 (51, 52), makes such studies more accessible.…”