Carbohydrate determinants of gangliosides commonly found in the central nervous system and cancer cells.

<p>CNS gangliosides: A. GT1b. B. GD1a. C. GD1b. D. GM1. Cancer-related gangliosides: E. GD2. F. GD3. G. GM3. H. Neu5Gc-GM3. Since each structure is differentiated by the removal of one or more residues from GT1b, the glycosidic linkages specified on GT1b apply to all of the structures, including Neu5Gc-GM3. Carbohydrate symbols follow the nomenclature of the Consortium for Functional Glycomics <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035457#pone.0035457-Nomenclature1" target="_blank">[63]</a>: <i>N</i>-acetylneuraminic acid – purple diamond; galactose – yellow circle; <i>N</i>-acetylgalactosamine – yellow square; glucose – blue circle; <i>N</i>-glycolylneuraminic acid – light blue diamond.</p

Evaluation of molecular docking using high resolution crystal structure complexes.

<p>A. Comparison of top ranked pose obtained from molecular docking (yellow) with the crystallographic binding mode (blue) of the Kdoα(2→4)Kdoα(2-OAll):S25-39 complex (PDB 3OKK). B. Comparison of top ranked pose (yellow) obtained from molecular docking with the crystallographic binding mode (blue) of the Kdoα(2→8)Kdoα(2→4)Kdoα(2-OAll):S73-2 complex (PDB 3HZV). C. Schematic representation of interactions in the Kdoα(2→4)Kdoα(2-OAll):S25-39 predicted by molecular docking. D. Schematic representation of interactions in the Kdoα(2→8)Kdoα(2→4)Kdoα(2-OAll):S73-2 complex. Molecular docking carried out using GOLD 4.1.1. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035457#pone-0035457-g002" target="_blank">Figures 2A and 2B</a> prepared using PyMOL <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035457#pone.0035457-Schrdinger4" target="_blank">[64]</a>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035457#pone-0035457-g002" target="_blank">Figures 2C and 2D</a> prepared using LIGPLOT <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035457#pone.0035457-Wallace1" target="_blank">[65]</a>. Legend to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035457#pone-0035457-g002" target="_blank">Figures 2C and 2D:</a> hydrogen bonds – green dashes; hydrophobic interactions – red arcs; carbon – black; oxygen – red; nitrogen – blue; ligand bonds – purple; protein bonds – orange.</p

Validation systems.

<p>Validation systems.</p

Molecular docking of validation systems.

a<p>Pose ranked first by molecular docking program.</p>b<p>Pose which gave the best RMSD value compared to the crystallographic binding mode. The docking rank is shown in parentheses.</p>c<p>No ligand poses were obtained following the docking procedure.</p

Peptide mimicry of GD2 binding to ME36.1.

<p>A. Hydrogen bonding site map describing peptide (LDVVLAWRDGLSGAS) recognition by ME36.1. B. van der Waals interaction site map describing peptide recognition by ME36.1. C. Comparison of hydrogen bonding site maps describing GD2 and peptide recognition. D. Comparison of van der Waals site maps describing GD2 and peptide recognition.</p

Conformer score for lowest energy conformers of chP3.

<p>Conformer score for lowest energy conformers of chP3.</p

Test systems.

a<p>Only peptide-based inhibitors are examined in the current study. Anti-idiotypic antibodies are included for reference.</p

Ganglioside recognition by test systems.^a

a<p>Percentage contribution to interactions shown only for residues identified as important for recognition by site mapping.</p>b<p>Results shown for HCDR3 conformer selected by dynamic site mapping.</p>c<p>By definition, these positions occur in CDR-adjacent framework regions.</p

Site maps of anti-ganglioside antibodies.

<p>Hydrogen bonding and van der Waals site maps of R24 (A and B), ME36.1 (C and D) and 14F7 (E and F). Residues contributing to the likely ganglioside-binding motif are labeled on the hydrogen bonding site maps.</p

Dynamic mapping of chP3.

<p>A. The second-lowest energy conformer, highlighting the stacking between the side-chains of Arg111.2H and Trp57H. B. The tenth-lowest energy conformer, predicted to be most likely to be involved in ligand binding. C. Hydrogen bonding site map for tenth-lowest energy conformer. D. The van der Waals map for tenth-lowest energy conformer. Residues contributing to the proposed ganglioside-binding motif are highlighted on the hydrogen bonding site maps.</p