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

Abstract

Computational model for GPI anchors tested in DMPC and POPC bilayers. The free anchor rarely occurs as an erected “lollipop-like” conformation, it rather “flops down” onto the bilayer surface. Yet an attached protein (here green fluorescent protein) exhibits extensive orientational flexibility due to the phospho-ethanolamine linker.

Coarse-Grained Molecular Model for the Glycosylphosphatidylinositol Anchor with and without Protein

“…GPI-Anchored GFP. We recall that from the all-atom simulations from our previous work 7 we could convincingly infer the following properties of the mutual interaction of the three different molecular species: (i) the GPI core undergoes similar conformational changes as if free in solution; (ii) the GPI core lies in close contact with the lipid head groups for both the free GPI and with the GPI-AP; (iii) the GPI core makes contacts with the attached protein; and (iiv) the EtNP- We now verify the aforementioned properties with our coarse-grained model. In Figure 17, we compare the structural properties, end-to-end distance, R ee , and radius of gyration, R g , of GPI when attached to GFP between the two resolutions.…”

“…Partial charges, angles, and torsions of this bridge were derived using quantum mechanical calculations, as described in our previous work. 7 We consider only pure DMPC lipid bilayer in this study, which was modeled with Lipid14. The lipid tail of the GPI is also a dimyristoyl.…”

“…The detailed methodology of the all-atom model development has been described in our previous paper. 7 Coarse-Grained. The coarse-grained GPI glycan was attached to a dimyristoyl lipid tail, the parameters of which were directly taken from the MARTINI lipid parameter set.…”

“…15−17 In our previous work, we devised an allatom model of GPI using GLYCAM06h, Lipid14, and AMBER-ff14SB force fields to elucidate the conformational flexibility of the glycan core in solution 18 and to study a full GPI-AP embedded in lipid bilayer patches. 7 Through plain and biased MD simulations, the GPI core was revealed to behave effectively as a hinge, with two rather rigid disaccharide units connected via a flexible Man-α(1→6)-Man linkage. With a lipid tail attached and inserted into a bilayer, GPIs tend to assume a hooklike conformation with the glycan core partially immersed in the lipid headgroup region.…”

“…A phosphoethanolamine linker (EtNP) attaches the protein to GPI. Ino+PGL are shown in blue to indicate the transition between the two force-field domains of GLYCAM06h (black) and Lipid14 (orange) that have been merged to provide a molecular model of the full structure.…”