Conformational Study of GPI Anchors: the Common Oligosaccharide GPI Anchor Backbone

Abstract

The solution three‐dimensional structure of pseudopentasaccharide 6, which constitutes the product from the GPI‐PLD cleavage of a GPI anchor, has been studied using a protocol which involves a systematic search of the conformational space around the glycosidic linkages, a thorough molecular dynamics study with explicit water molecules and a full NMR analysis study of intramolecular hydrogen bonding in solution. The results indicate that 6 exists in an extended conformation with a considerable flexibility compatible with a hinge‐like conformational motion. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

A molecular dynamics model for glycosylphosphatidyl-inositol anchors: “flop down” or “lollipop”?

“…Homans et al gave an early structural account of the GPI anchor covering the surface of Trypanosoma brucei, 15 Zuegg and Gready 28 investigated the flexibility of an isolated prion protein attached to a simplified model of a lipid monolayer. Lomás and coworkers have studied the conformational characteristics of the GPI core, 23 and that of isolated GPI anchors inserted in small micelles, 24 with short simulations in support of NMR data.…”

“…Exploring molecular scale details of GPI placement, however, even with elaborate NMR approaches inevitably requires computational methodology. [23][24][25] With the present work we want to study the embedding of GPI anchors in lipid bilayers with atomistic, molecular dynamics (MD) simulations. To facilitate modular buildup and accurate representation of either molecular species, we shall construct a hybrid computational model by combining two state-ofthe-art force fields from the AMBER family, GLYCAM06 26 (glycans) and Lipid14 27 (lipids).…”

Influence of tissue maturation and antioxidants on the apoptotic response of articular cartilage after injurious compression

“…However, it was not possible to define a unique conformation for 30 , which exists in an extended conformation that undergoes large torsional oscillation about the Manα1→6Man linkage with fluctuations of hydroxyl groups on a picosecond timescale 89c. Studies of lipidated GPI anchor 31 incorporated into micelles revealed that the structural properties of the glycan are similar to those of 30 ,89d in addition to the complex dynamic behavior with a faster relative motion at the terminal mannose residue and decreased mobility close to the micelle 89e. This result implies that the intrinsic behavior of GPI anchors does not change through the vicinity of the lipid–water interface, and molecular dynamics might be a suitable tool for the prediction of the conformational behavior of GPIs in solution.…”

GLYCAM06: A generalizable biomolecular force field. Carbohydrates

“…The derivation of a highly consistent and transferable parameter set for modeling carbohydrates and glycoconjugates (GLYCAM06) is the focus of the present work. In light of accumulated applications of GLYCAM_93,10, 22–25, 27–31, 43–48 several areas were targeted for improvement. In particular, the parameter set should (1) be transferable to all carbohydrate ring conformations and sizes, (2) be self‐contained and therefore readily transferable to many quadratic force fields, (3) not require specific atom types for α‐ and β‐anomers, (4) be readily extendible to carbohydrate derivatives and other biomolecules, (5) be applicable to monosaccharides and complex oligosaccharides, (6) be rigorously assessed in terms of the relative accuracy of its component terms, and (7) avoid the use of 1–4 electrostatic or non‐bonded scaling factors 24.…”