A molecular dynamics approach for the association of apolipoproteinB-100 and chondroitin-6-sulfate.

A force field has been previously designed for a dodecasaccharide chain of chondroitin-6-sulfate (C6S) and has proved to yield valuable data going from basic conformational properties to a more detailed H-bonding network. This force field is further used here to unravel the interaction of C6S with its pathological counterpart in low density lipoprotein (LDL) particles. In particular, well-selected peptide fragment p2 (residues 3359-3377) also identified as the principal proteoglycan binding site (PPBS) of the major protein in LDL, apolipoproteinB-100 (apoB-100), was chosen. We study here the interaction between C6S and p2. The role of arginine and lysine, positively charged amino acids of p2, in the crucial interaction of C6S with LDL is highlighted. The secondary structure of p2 is shown to affect the efficiency of the interaction, as the α-helical structure of p2 allows optimal interaction with C6S also in dynamic conditions. One point mutation in p2 appeared to affect consequently p2-C6S interaction.

Atomistic insight into chondroitin-6-sulfate glycosaminoglycan chain through quantum mechanics calculations and molecular dynamics simulation.

Chondroitin-6-sulfate (C6S) is a glycosaminoglycan (GAG) constituent in the extracellular matrix, which participates actively in crucial biological processes, as well as in various pathological conditions, such as atherosclerosis and cancer. Molecular interactions involving the C6S chain are therefore of considerable interest. A computational model for atomistic simulation was built. This work describes the design and validation of a force field for a C6S dodecasaccharide chain. The results of an extensive molecular dynamics simulation performed with the new force field provide a novel insight into the structure and dynamics of the C6S chain. The intramolecular H-bonds in the disaccharide linkage region are suggested to play a major role in determining the chain structural dynamics. Moreover, the unravelling of an additional H-bond involving the sulfate groups in C6S is interesting as changes in sulfation have been claimed to be an important factor in several diseases. The force field will prove useful for future studies of crucial interactions between C6S and various nanoassemblies. It can also be used as a basis for modeling of other GAGs.

Modelling of ceramide interactions with porous graphite carbon in non-aqueous liquid chromatography.

Interactions of solutes on porous graphitic carbon (PGC) with non-aqueous mobile phases are studied by the linear solvation energy relationship (LSER). Studies have been carried out with eight binary mixtures composed of a weak solvent (acetonitrile or methanol) and a strong solvent (tetrahydrofuran, n-butanol, CH2Cl2, 1,1,2-trichloro-2,2,1-trifluoroethane). The systematic analysis of a set of test compounds was performed for each solvent mixture in isocratic mode (50:50). The results were compared to those obtained on PGC with hydro-organic liquids and supercritical fluids. They were then correlated with the observed retention behaviour of lipid compounds, more particularly ceramides.