Characterization of the conformational and orientational dynamics of ganglioside GM1 in a dipalmitoylphosphatidylcholine bilayer by molecular dynamics simulations

Abstract

The structure and dynamics of a single GM1 (Gal5-beta1,3-GalNAc4-beta1,4-(NeuAc3-alpha2,3)-Gal2-beta1,4-Glc1-beta1,1-Cer) embedded in a DPPC bilayer have been studied by MD simulations. Eleven simulations, each of 10 ns productive run, were performed with different initial conformations of GM1. Simulations of GM1-Os in water and of a DPPC bilayer were also performed to delineate the effects of the bilayer and GM1 on the conformational and orientational dynamics of each other. The conformation of the GM1 headgroup observed in the simulations is in agreement with those reported in literature; but the headgroup is restricted when embedded in the bilayer. NeuAc3 is the outermost saccharide towards the water phase. Glc1 and Gal2 prefer a parallel, and NeuAc3, GalNac4 and Gal5 prefer a perpendicular, orientation with respect to the bilayer normal. The overall characteristics of the bilayer are not affected by the presence of GM1; however, GM1 does influence the DPPC molecules in its immediate vicinity. The implications of these observations on the specific recognition and binding of GM1 embedded in a lipid bilayer by exogenous proteins as well as proteins embedded in lipids have been discussed.

CHARMM-GUI Membrane Builder for Complex Biological Membrane Simulations with Glycolipids and Lipoglycans

“…Consequently, there are much fewer simulation studies using glycolipids/lipoglycans compared to those with phospholipids. Previous glycolipid computational studies used structures based on those available from the PDB 11,12 , coarse-grained (CG) models 13,14 , or model structures generated via complicated ways [15][16][17][18] . However, the glycolipid/lipoglycan types available in the PDB or CG models are limited, and a customized building procedure is often arduous to follow.…”

Clustering effects of GM1 and formation mechanisms of interdigitated liquid disordered domains in GM1/SM/CHOL-supported planar bilayers on mica surfaces

“…As for the structural analysis with lipid bilayers, nuclear magnetic resonance (NMR) [9], neutron scattering [10] and molecular dynamics (MD) computer simulation [11][12][13] have also made important contributions.…”

Ganglioside Influence on Phospholipid Films Investigated with Single Molecule Fluorescence Measurements

“…This charge contributes to the electrostatic potential of the membrane and can influence the orientation of nearby BODIPY-PC probe molecules through electrostatic interaction. 38 To confirm that nearby charged headgroups can alter BODIPY-PC orientation, studies in mixed monolayers of DPPC and negatively charged DPPS were conducted. As shown in Figure 1, DPPS contains a negatively charged serine group but is otherwise structurally similar to DPPC.…”