Computer modeling of hydrophilic monomer adhesion to hydroxyapatite

Hydrophilic monomers are used to prime tooth tissues during bonding. The interaction between these primer ligands and hydroxyapatite phase are especially important in self-etch adhesives. Recent studies have shown ionic interaction between self-etch primers and hydroxyapatite phase of tooth tissues. Objective: The goal in this study was to computer model the interactions between hydroxyapatite (HAP) and hydrophilic monomers using ligand-target docking simulations. Materials and Method: Sybyl (Tripos) molecular modeling program was used to generate geometry optimized, energy minimized 3-D monomer ligand structures of selected metahcrylated phosphates (MDP and PhenylP). The ligands were treated in their deprotonated states. AutoDock version 4 (Scripps Research Institute) was used for docking studies. The HAP target structure was modeled by refining the RCSB PDB file 35s02. Lamarckian genetic algorithm was used for docking simulations. Total binding energy (BE) was determined as the algebraic sum of electrostatic energy (EE) and other energies of interaction. Ten docked conformations for each ligand have been initially characterized. Typical docked conformations were visualized to determine target and ligand docking sites. A calcium-binding phosphoserine-glutamic acid peptide served as a control. Results: BE (kcals/mole) ranged between –63.13 to –64.84 (MDP) and –34.55 to –36.52 (PhenylP). EE (kcals/mole) ranged between –72.32 to –74.67 (MDP) and –38.52 to –40.09 (PhenylP). The interaction of control peptide to HAP was stronger (BE: –70.86 to –77.97/EE: –80.34 to –88.46). The ligand conformations typically docked with the phosphate functionality bonded to Calcium sites in HAP. The results revealed high electrostatic interaction between HAP and dentin methacrylate phosphate adhesives (MDP and PhenylP) and statistically significant differences between interaction energies of MDP and PhenylP (p<<0.05). Electrostatic interaction was the dominant energy contribution. Conclusions: The results suggest that docking simulations can be used to screen adhesives for bonding to HAP phase. Supported by NIH/NIDCR grant DE14370.