Dental Adhesive Monomer Interactions With Cariogenic Enzymes: Integrated Docking, DFT, and GtfI‐Focused Molecular Dynamics Analysis
Ravinder S. Saini, Abdullah Hassan A. Alshehri, Rayan Ibrahim H. Binduhayyim, Abdulkhaliq Ali F. Alshadidi, Syed Altafuddin Quadri, Abdulmajeed Okshah, Ahid Amer Alshahrani, Mohamed Saheer Kuruniyan, Vishwanath Gurumurthy, Masroor Ahmed Kanji, Artak HeboyanAim
The purpose of this in silico research study was to examine three frequently used dental adhesive monomers (10‐methacryloyloxydecyl dihydrogen phosphate, 10‐MDP; bisphenol A‐glycidyl methacrylate, Bis‐GMA; urethane dimethacrylate, UDMA) for their molecular interactions with key cariogenic enzymes in an attempt to determine possible biointeractive/enzyme‐modulating behavior at a molecular level.
Methods
A combined in silico workflow was utilized, including molecular docking, density functional theory (DFT) calculations, molecular dynamics (MD) simulations, MM/PBSA binding free‐energy analysis, and per‐residue energy decomposition analysis. Molecular docking was performed to screen monomer binding to a panel of cariogenic enzymes. Electronic, energetic, and dynamic analyses were further applied to characterize the top‐ranked complexes.
Results
Docking results revealed that glucosyltransferase I (GtfI), fructose‐bisphosphate aldolase (FBA), and alanine racemase (Alr) maintained a favorable binding pattern for all three monomers and were selected for detailed interaction studies. DFT results revealed that both 10‐MDP and UDMA had lower HOMO–LUMO gaps (5.87 and 5.90 eV, respectively), as well as higher dipole moment values, indicating higher polarity and ability to interact, while Bis‐GMA had the highest electronic stability (gap value: 8.88 eV). As GtfI enzymes play a key role in the synthesis of glucan as well as the development of the biofilm matrix, it was chosen as the target enzyme for MD and MM/PBSA studies. MD and MM/PBSA analyses of GtfI revealed that 10‐MDP and Bis‐GMA maintained a more stable dynamic occupancy with moderate predicted binding affinities compared to UDMA.
Conclusion
Targets associated with caries demonstrated enzyme‐selective, chemistry‐dependent binding interactions with dental adhesive monomers. Further dynamic simulations of other targets will be required to confirm the hypothesis generated by detailed GtfI simulations that 10‐MDP and Bis‐GMA may modulate GtfI‐mediated behavior. These data offer a hypothesis‐driven theoretical foundation for further investigation into multipurpose dental materials possessing potential enzyme‐altering anticariogenic mechanisms.