Identification of candidate ligands for quantum dot-functionalized prosthetic biomaterials targeting Porphyromonas gingivalis gingipain RgpB: a molecular docking study

Porphyromonas gingivalis is an important periodontal pathogen associated with peri-implant and prosthesis-related infections, and its gingipains contribute to bacterial pathogenicity and tissue damage. Strategies that limit gingipain activity or bacterial colonization on prosthetic biomaterials, therefore, have potential clinical relevance. However, the interaction of gingipains with surface-functionalizing molecules proposed for nanostructured dental materials has not been sufficiently characterized at the molecular level. The purpose of this in silico study was to comparatively evaluate the interaction of Arg-specific gingipain RgpB with nine small-molecule ligands proposed as potential surface-functionalizing agents for quantum dot (QD)-based coatings. The study aimed to identify candidate ligands with favorable predicted RgpB interactions as an initial step toward the development of nanostructured prosthetic biomaterials with potential relevance to limiting P. gingivalis-associated pathogenic mechanisms. Molecular docking was performed using AutoDock Vina (v.1.2.0) with the 2.00-Å crystal structure of the catalytic domain of RgpB (PDB: 1CVR). Nine ligands gallic acid, caffeic acid, p-aminobenzoic acid, catechol, citric acid, L-tartaric acid, succinic acid, 3-aminopropylamine, and ethylenediamine were evaluated. Ligand structures were retrieved from PubChem, energy-minimized using the MMFF94 force field in Open Babel (v.3.1.1), and prepared for docking with flexible ligand torsions and a rigid receptor. The docking region was centered on the Cys244-His211 catalytic region, with an exhaustiveness value of 32. Ten independent docking runs were performed for each ligand. The lowest-energy pose from each run was used for comparative analysis. Mean docking scores, standard deviations, and 95% confidence intervals were calculated, and differences among ligand groups were assessed using one-way analysis of variance followed by Tukey’s honestly significant difference test. Predicted ligand-residue interactions were additionally evaluated using LigPlot+ (v.2.2). Mean docking scores ranged from − 5.62 ± 0.28 kcal/mol for caffeic acid to -2.92 ± 0.18 kcal/mol for ethylenediamine. Gallic acid and caffeic acid demonstrated the most favorable predicted docking scores, whereas ethylenediamine and 3-aminopropylamine showed the weakest predicted docking scores. Overall differences among ligands were statistically significant (one-way ANOVA, F = 149.7, p < 0.001). Gallic acid and caffeic acid formed multiple predicted hydrogen-bonding and π-related interactions with residues located within or near the RgpB catalytic region, including Tyr283, His211, Gln282, and Trp284. Carboxylate-containing ligands demonstrated intermediate predicted binding scores. The in silico analysis results revealed that gallic acid and caffeic acid showed the most favorable predicted interactions with RgpB among the evaluated ligands. These findings support the potential of phenolic ligands as candidate surface-functionalizing molecules for the development of QD-based prosthetic biomaterials targeting P. gingivalis-associated pathogenic mechanisms. The observed ligand-RgpB interactions provide a molecular basis for prioritizing these compounds in subsequent studies of functionalized dental materials and may contribute to the rational design of prosthetic surfaces with potential anti-virulence and anti-biofilm properties.