Effect of Structural Variability of the Ceramide Part on the Saccharide-Ceramide Linkage in Model Glycolipids Studied by Molecular Mechanics and Molecular Dynamics Methods

Abstract

Conformational analysis was performed for model glycosphingolipid molecules with a view to studying the effect of structural variability of the lipidic part and its flexibility on the saccharide-ceramide linkage. In addition to systematic and random molecular mechanics sampling techniques (the RAMM program), molecular dynamics simulations (Biosym DISCOVER program) were carried out to analyze the conformational energy surface of the model glycolipid molecules. The influence of the structural variability and flexibility of the lipidic part is demonstrated by prediction of the stability of different conformations around the carbohydrate-ceramide linkage. The α2, α1 and Θ1 torsional angles are the most important structural parameters with respect to the carbohydrate-ceramide connection. Two dominant conformations for the saccharide-ceramide linkage were observed, with the α2/α1/Θ1 dihedral angles in the -sc/+ac/ap and -sc/ap/-sc regions. While each of the calculation methods predicts similar flexibility in the α2/α1 space, the flexibility around the Θ1 angle differs considerably, reflecting the parametrization and set-up of the modelling protocol.