The objectives of this investigation were to analyze the adhesive interactions between type 1 collagen and two hydrophilic monomer primers (ligands) for dentin bonding through computer modeling and a novel immunochemical binding assay method. The hydrophilic monomers studied included 2-hydroxyethyl methacrylate (HEMA) and 2-acryloyloxyethyl phosphate (PA). For computer modeling studies, a triple helical model structure of collagen fibril extracted from a public domain Protein Data Bank was used. The ligand conformations were modeled and optimized by Sybyl, and their interactions with the triple helical collagen structure in a solvent environment of water were simulated by AutoDock software. The effect of ligand binding to subsequent monoclonal antibody binding was also studied using an immunochemical binding assay method developed by us. The computer simulation results and binding assay results were analyzed for relationships pertinent to collagen-ligand interaction in bonding of dentin primers to demineralized dentin. Computer docking results indicate that ligand binding to collagen is favored to occur at cavity sites on the collagen molecular surfaces, where steric and electrostatic effects may play a critical role in mediating van der Waals and Coulombic interactions between ligand and receptor molecules. Prior ligand exposure of collagen reduces subsequent antibody binding during in vitro experiments. Differences in antibody binding were observed both as a function of ligand type and its concentration. Both steric complementarity and electrostatic complementarity conditions were observed in the docking site selection. Under conditions of ligand binding, antibody binding is diminished as a function of ligand structure and its concentration. The results suggest that approaches combining computer modeling and in vitro binding assay methods are powerful tools in evaluating dentinal adhesion at the atomic and/or molecular level.