Molecular docking and dynamics simulation of antimicrobial peptides against adhesion proteins of peri-implant pathogens

Abstract Peri-implantitis is a major cause of late implant failure and is closely associated with biofilm formation by anaerobic pathogens such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. These bacteria express adhesion proteins, including FimA and BspA, which facilitate initial colonization on implant surfaces. LL-37 and Tachystatin A2, which have previously demonstrated antimicrobial activity against these pathogens, were selected for evaluation in this study. The objective was to investigate the potential of selected antimicrobial peptides (AMPs)—LL-37, Tachystatin A2, and a Thermolysin-derived peptide fragment—as inhibitors of bacterial adhesion proteins using molecular docking and molecular dynamics (MD) simulations. The Thermolysin-derived fragment refers to a short peptide sequence from the Thermolysin metalloprotease, specifically designed and selected for this purpose rather than the full-length enzyme. Three-dimensional structures of FimA and BspA were obtained from the RCSB Protein Data Bank or generated via homology modeling. AMP structures were retrieved or modeled and subsequently energy-minimized. Molecular docking was performed using AutoDock Vina, followed by 100-nanosecond MD simulations in GROMACS to assess the stability of peptide–protein interactions. Binding stability was evaluated through root-mean-square deviation (RMSD), hydrogen bond analysis, and MM-PBSA binding energy calculations. Preliminary in silico findings suggest that LL-37 and Tachystatin A2 exhibit strong and stable binding to FimA and BspA, highlighting their potential as candidates for functionalizing implant surfaces to reduce bacterial adhesion. These results warrant further experimental studies to validate AMP-based anti-biofilm strategies in dental implantology.