Computational analysis of adhesion of primer ligands to dentinal collagen: effect of spacer groups in ligand and amino Acid residue sequence differences in collagen.

This study sought to assess by computer modeling the interactions between dentinal collagen and primer monomer ligands used to promote bonding of restorations to tooth. Modeling was carried out both by direct and indirect methods to probe interaction mechanisms. Ligands studied in this investigation conformed chemically to methacrylate phosphates of alkane diol, with changes in the number of methylene spacer groups. Increase in number of methylene groups in the series introduces increasing levels of ligand conformational freedom. An automatic docking program was used to analyze the effect of these changes on primer-collagen interactions in direct (target-based) modeling. The effect of limited modifications of amino acid residue sequences in structural variants of type 1 dentinal collagen was also assessed in this approach. The indirect (ligand-based) modeling used a pharmacaphore search to mimic primer binding to type 1 collagen using a common functional alignment algorithm. Docking energy, and the non-bonded and electrostatic contributions to it, showed statistically highly significant differences (p<0.0001) with ligand conformational freedom. But the effect of collagen composition differences was, although statistically significant (p<0.05), relatively small. Both target-based direct docking and ligand-based indirect modeling visualizations showed that conformations tended to align in a 3-D geometric pattern in bound states, and that the conformational flexibility of the ligands played a critical role in alignment. The results suggest that incorporation of spacer groups in primer monomers may modify dentin bonding to improve overall adhesion under optimum conditions.