The strength, durability and impermeability of the dentin-restoration interface are of critical importance during tooth restoration because any post-restoration breakdown of this interface opens up pathways for toxins and bacteria to penetrate into the pulp. In recent years, there has been considerable focus on the formation of hybridized dentin at this interface by the infiltration of adhesives into the dematerialized dentin during bonding. Analytical and morphological studies have revealed the hybrid layer to be an intimate molecular mixture of collagen fibrils and adhesive material. During bonding adhesive monomers are allowed to permeate into the vacant spaces on the subsurfaces of dentin opened up by demineralization. During infiltration into the sub-surface of dentin, the monomer interacts with collagen fibrils and is subsequently polymerized to provide strength to the hybridized structure. Spectrographic investigations have not been able to fully characterize the interface structure, especially the adhesive-collagen interaction. Different investigators have arrived at conflicting conclusions based on similar or different experiments. One innovative approach to study hybridized dentin is to probe potential interactions through computer simulations. The research outlined in this application is a continuation of a novel method of computer-aided biomimetic modeling of collagen and monomer structures and their interactions. The applicant developed this method in a feasibility study supported by the NIH through an AREA grant. In this study, optimized conformational states of model structures of the triple helical collagen receptor and the monomer molecules and the complex generated by their interaction will be visualized and their interactions in the presence of a solvent analyzed at the atomic level. The steric and electrostatic complementarity of the reactive sites of the ligand receptor molecules will be characterized. The interaction energy for the formation of the collagen-ligand complex will be calculated as the cumulative effect of van der Waals, electrostatic and hydrogen bonding interactions. These energy contributions will be analyzed to determine the predominant mode of interaction for each monomer. Binding studies between the ligands and collagen will be conducted by:1) a novel immunochemical binding assay developed by us; and 2) isothermal titration calorimetry, and related to computed interaction energy values.
