Molecular Recognition of Dental Resin Monomers by Salivary Proteins: Integrated Docking, DFT, Molecular Dynamics, and MM/PBSA Analysis

An in silico investigation was performed to study the interactions between the commonly encountered resin monomers and the major salivary proteins. Bisphenyl diglycidylmethane (Bis‐GMA), hydroxyethyl methacrylate (HEMA), and triethylene glycol dimethacrylate (TEGDMA) were assessed for molecular docking, density functional theory (DFT), molecular dynamics (MD), MM/PBSA binding free‐energy calculations, and per‐residue energy decomposition. α‐amylase, lysozyme, and albumin emerged as critical predicted targets from the docking process. DFT calculations found Bis‐GMA to possess the largest HOMO–LUMO gap (8.88 eV), suggestive of reduced electronic reactivity, and TEGDMA to have the smallest gap (5.56 eV) as well as the largest dipole moment (3.88 D), indicative of increased polarity. Mean solvent accessible surface areas (SASAs) determined through MD trajectories suggest a trend of increased conformational stability with Bis‐GMA. More favorable mean MM/PBSA predicted binding free energies were calculated with Bis‐GMA, especially with albumin (−24.53 ± 5.12 kcal/mol) and α‐amylase (−17.63 ± 7.60 kcal/mol). Residue‐decomposition heatmaps displayed mixed favorable and unfavorable contributions, which were interpreted descriptively. Recognition of monomers by salivary proteins appears to correlate with molecular dimensions, hydrophobicity, polarity, and electronic properties. These observations are preliminary calculations that require experimental evidence to reach clinical or functional conclusions.