Structural Bioinformatics Analysis of the Allicin-DNA Gyrase Interaction: Computational Evidence and Optimization Insights

Objective: To elucidate the noncovalent binding features and dynamic stability of allicin with bacterial DNA gyrase (PDB ID: 6RKS). Methods: The co-crystallized binding pocket was targeted for docking with AutoDock Vina, followed by 100 ns explicit-solvent molecular dynamics simulations using Schrödinger 2024 (Desmond; OPLS4/TIP3P). Interaction occupancies and contact heatmaps provided quantitative analysis. Results: Docking showed extensive hydrophobic interactions of allyl groups with Pro164, Val190, Cys194, Ile351, and Phe354. The thiosulfinate moiety formed hydrogen bonds with Thr161 and Leu166/167. MD simulations revealed a repositioning event at ~50-52 ns from a shallow site into a deeper subpocket, indicated by increased ligand and complex RMSD, decreased ligand radius of gyration, reduced solvent-accessible surface area, and increased polar surface area. Persistent anchors included Phe354 and Val190, with a time-ordered interaction shift (Ile351→Ile350, Leu167→Leu166) and additional Pro164 contacts. Protein RMSF remained low, indicating local pocket adaptation. Conclusion: Allicin binds stably through hydrophobic encapsulation and backbone-polar anchoring, with a key repositioning around 50 ns establishing the steady-state pose. These findings offer a basis for optimizing allicin derivatives and designing DNA gyrase inhibitors, with further experimental validation needed for potential covalent reactivity.