3D-free energy representations of systems Sy1, Sy2, Sy3, Sy12, Sy13 and Sy14.

<p>Each isosurface corresponds to points of the 3D-space (φ_x, φ_y, φ_z) with a constant free energy isovalue of 5.4 kcal.mol⁻¹ (9 k_BT); replica II (240 ns) at T = 300K.</p

Structure and numbering of the ligands involved in the studied systems.

<p>Structure and numbering of the ligands involved in the studied systems.</p

Root mean square fluctuation and 1D-FEL dissimilarity of H_aGAL and H_CD1d systems.

<p>(A) per residue RMSF (Å) of binary complexes H_aGAL and H_CD1d for replica III; color scale (from blue to red) is proportional to the fluctuation (B) 1D-FEL dissimilarity for each coarse-grained dihedral angle along the main chain between binary complexes H_aGAL and H_CD1d (replica III); color scale (from blue to red) is proportional to the dissimilarity measured by a Hausdorff-like distance (unit mixing the energy and angle axes); the free energy profiles of the six residues the most influenced by the presence of <b>1</b> are emphasized below the protein; units are k_BT (energy) and degrees (angles).</p

Inter-helix distance and dihedral deviation index.

<p>Left: inter-helix distance measured as the distance between centroids of α₁ and α₂ helices; Right: deviation from the interface X-ray structure based on TCR-CD1d contacts dihedrals; lipid-free CD1d (black) and <b>1</b> loaded CD1d (blue); replica II.</p

(CD1d-1)-TCR footprint.

<p>Reduced density gradient isosurfaces (blue, s = 0.6) provide a meaningful visualization of non-covalent interactions (NCI) as wide regions of molecular space in the TCR-CD1d binding domain; for the sake of clarity, these surfaces are not colored according to the strength of the interaction.</p

CD1d inter-helix distances for H_NUaGAL, M_NUaGAL, H_7DW and M_7DW systems.

<p>This distance is measured as the distance between centroids of α₁ and α₂ helices; Replica I.</p

List of 16 various systems involving human or mouse CD1d and up to eight different ligands.

<p>List of 16 various systems involving human or mouse CD1d and up to eight different ligands.</p

Root mean square deviation matrix of H_aGAL (top) and H_CD1d (bottom) simulations.

<p>Root mean square deviation (alpha carbons of CD1d α₁/α₂ helices) of every conformation to all other as a function of time during a 240 ns simulation; replica I, II, III.</p

3D-FEL associated to the polar head conformations for the H_aGAL system.

<p>Left: <b>1</b> loaded human CD1d with the OTAN hydrogen bond network emphasized and the three torsion angles for the polar head to be rotated. Right: 3D-free energy representations of H_aGAL system <b>1</b> (replica I, T = 300K); each of the nine isosurfaces corresponds to points of the 3D-space (φ_x, φ_y, φ_z) with a constant free energy isovalue (in kcal.mol⁻¹); the three last boxes correspond to the three isosurfaces (2.7 kcal.mol⁻¹) obtained for the three replicas (240 ns each).</p

Switching Invariant Natural Killer T (iNKT) Cell Response from Anticancerous to Anti-Inflammatory Effect: Molecular Bases

Since the discovery in 1995 of α-galactosylceramide <b>1</b> (α-GalCer), also known as KRN7000, hundreds of compounds have been synthesized in order to activate invariant natural killer T (iNKT) cells. Such keen interest for this lymphocyte cell type is due to its ability to produce different cytokines that bias the immune response toward a Th1 or Th2 profile. Thus, an understanding of the immune polarization mechanism via iNKT activation may pave the way toward new therapeutics in various domains including cancer and infectious and autoimmune diseases. In this review, we propose an up-to-date analysis of iNKT activators associated with a structure–activity relationship (SAR) study aimed at complementing available reviews by highlighting molecular bases for a selective immune response