Radial distribution function for three carbon atoms along the alkyl chain for monoalkylated lipids: (a) βMal-C₁₂ (b) βCel-C₁₂ and (c) βIsoMal-C₁₂.

<p>Radial distribution function for three carbon atoms along the alkyl chain for monoalkylated lipids: (a) βMal-C₁₂ (b) βCel-C₁₂ and (c) βIsoMal-C₁₂.</p

Correlation times as a function of each C–H vector along lipid alkyl chains are shown.

<p>The labeling of carbon atoms follows the naming convention as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101110#pone-0101110-g001" target="_blank">Figure 1</a>. (a) shows the correlation times for monoalkylated glycolipids, <i>β</i>Mal-C₁₂ (<b>+</b>), <i>β</i>Cel-C₁₂ (<b>×</b>), and <i>β</i>IsoMal-C₁₂ (*). (b) and (c) show correlation times for chains <i>sn-1</i> and <i>sn-2</i> respectively for <i>β</i>BCMal-C₁₂C₁₀.</p

Some lipids' conformations and bilayer snapshots from the simulation.

<p>(a) Three possible lipid conformations with the chain tilt angle, θ of 24° and 156°. (b) The dispersion interaction observed from two viewing angles, between the C–H from the sugar face and those of the alkyl chain by a representative lipid (enlarged) from the third layer. (c) A characteristic example of the sugar headgroup region (t = 140 ns) from the third leaflet showing the hydrophobic cavity (top-view). (d) The time evolution of a typical side-view of the second and third leaflets. The lipid (drawn fully with VDW model) is seen to work itself into the hydrophilic region.</p

Fractional <i>gauche</i> population in, <i>P</i>(<i>gauche</i>), for dihedral angles between carbons in the alkyl chains.

<p>The dihedral angle label, for example C71–C74 represent C71–C72–C73–C4 following alkyl chain numbering in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101110#pone-0101110-g001" target="_blank">Figure 1</a>. (a) <i>β</i>Mal-C₁₂, (b) <i>β</i>Cel-C₁₂, (c) <i>β</i>IsoMal-C₁₂, (d) <i>β</i>BCMal-C₁₂C₁₀(<i>sn-1</i>), and (e) <i>β</i>BCMal-C₁₂C₁₀(<i>sn-2</i>). First lipid layer (□), second layer (×), third layer (+), and fourth layer (*).</p

Glycosides used in the simulation: (a) <i>β</i>Mal-C₁₂ (b) <i>β</i>Cel-C₁₂ and (c) <i>β</i>IsoMal-C₁₂ (d) <i>β</i>BCMal-C₁₂C₁₀.

<p>Starting from glycosidic oxygen, each glycolipid's main alkyl chain (<i>sn-1</i>) is labeled from C71 to C82 and the branched chain (<i>sn-2</i>) from C83 to C92. Here, for clarity we have reduced the atoms' labels on the sugar, a slight modification from the standard nomenclature according to IUPAC given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101110#pone-0101110-g001" target="_blank">Figure 1</a> of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101110#pone.0101110-ManickamAchari1" target="_blank">[22]</a>.</p

Snapshot of chain vectors between midpoints of C71–C72 and C80–C81 for monoalkylated lipids and chain <i>sn-1</i>.

<p>For chain <i>sn-2</i>, the vector is defined between midpoints of C71–C72 and C90–C91.</p

Average correlation time of sugar headgroup of lipids: reducing sugar (<i>ring1</i>); non-reducing sugar <i>(ring2)</i>; and combination of <i>ring1</i> and <i>ring2</i> (<i>ring12</i>).

<p>Average correlation time of sugar headgroup of lipids: reducing sugar (<i>ring1</i>); non-reducing sugar <i>(ring2)</i>; and combination of <i>ring1</i> and <i>ring2</i> (<i>ring12</i>).</p

Distributions of alkyl chain tilt angle θ of various glycolipids for one layer.

<p>Shows the current results for 160<i>β</i>Mal-C₁₂, black for <i>β</i>BCMal-C₁₂C₁₀ (<i>sn-1</i>), deep sky blue for <i>β</i>BCMal-C₁₂C₁₀(<i>sn-2</i>), green for <i>β</i>Cel-C₁₂ and dark blue for <i>β</i>IsoMal-C₁₂.</p

Identification of rare Lewis oligosaccharide conformers in aqueous solution using enhanced sampling molecular dynamics

<p>Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate the conformational free energy surfaces of Lewis oligosaccharides in explicit aqueous solvent using a multidimensional variant of the swarm-enhanced sampling molecular dynamics (msesMD) method; we compare with multi-microsecond unbiased MD simulations, umbrella sampling and accelerated MD approaches. For the sialyl Lewis A tetrasaccharide, msesMD simulations in aqueous solution predict conformer landscapes in general agreement with the other biased methods and with triplicate unbiased 10 ms trajectories; these simulations find a predominance of closed conformer and a range of low occupancy open forms. The msesMD simulations also suggest closed-to-open transitions in the tetrasaccharide are facilitated by changes in ring puckering of its GlcNAc residue away from the ⁴C₁ form, in line with previous work. For sialyl Lewis X tetrasaccharide, msesMD simulations predict a minor population of an open form in solution, corresponding to a rare lectin-bound pose observed crystallographically. Overall, from comparison with biased MD calculations, we find that triplicate 10 ms unbiased MD simulations may not be enough to fully sample glycan conformations in aqueous solution. However, the computational efficiency and intuitive approach of the msesMD method suggest potential for its application in glycomics as a tool for analysis of oligosaccharide conformation.</p

Ramachandran plots of the distribution of the (φ, ψ) backbone dihedrals of residues 1–15 for peptides WT, I, R and RI, calculated over of the 50 ns REMD trajectories.

<p>Ramachandran plots of the distribution of the (φ, ψ) backbone dihedrals of residues 1–15 for peptides WT, I, R and RI, calculated over of the 50 ns REMD trajectories.</p