A computational approach to explore the binding mechanism of secondary metabolites of Hamigera ingelheimensis with AgrA quorum sensing proteins

Bacterial resistance to existing antibacterials can be handled by focusing on the bacterial communication system, specifically bacterial quorum sensing system. Inhibiting AgrA‐DNA binding is an effective strategy for reducing the expression of diverse genes involved with the secretion of virulence factors by the Agr quorum sensing system. Hamigera ingelheimensis, a common soil fungus, produces several bioactive secondary metabolites including avellanin C which is a well‐recognised and deeply studied quorum sensing inhibitor. Among the several metabolites, we selected ten metabolites and other metabolites have been rejected either some of them were exhaustively studied or during primary docking screening, they did not show promising docking scores. These ten metabolites were docked with template protein (PDB ID: 4G4K) and with five homologies modelled AgrA proteins using AutoDock tool. Avellanin A, avellanin B and PF1171B showed a promising binding score with all the proteins with binding free energy less than ‐8.00 kcal.mol‐1. Molecular dynamics simulations suggest that their docked complexes are stable. These three metabolites have drug‐likeness features and thus have the tremendous prospect to be used as the AgrA inhibitors.