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 an increased ligand and complex RMSD, a decreased ligand radius of gyration, a reduced solvent-accessible surface area, and an increased polar surface area. Persistent anchors included Phe354 and Val190, with a time-ordered interaction shift (Ile351 → Ile350, Leu167 → Leu166) and additional Pro164 contacts. The 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.