Unlocking the therapeutic potential of phytocompounds from essential oils of Melaleuca alternifolia and Rosmarinus officinalis targeting bacterial penicillin-binding proteins by computational and experimental validation

A major issue is the unchecked use of currently available antibiotics, which has caused microorganisms all around the world to become resistant to them. To solve this issue, it is thus required to use computational biochemistry to find and create novel antibacterial chemicals with fresh formulations. One potential target for creating therapeutic medications is penicillin-binding proteins (PBPs). Essential oils of tea tree (TEO) and rosemary (REO) have several biological benefits, including immunomodulation, anticancer, antibacterial, and antifungal characteristics. This work aimed to investigate the molecular docking of TEO and REO bioactive components against seven bacterial PBPs (PBP1a, PBP2a, PBP2X, PBP3, PBP4, PBP5, and PBP6) on in vitro support. Cb-dock2, a docking tool, was utilized. The in-silico bioprospecting of every ligand included an ADMET pharmacoinformatic aspect (physicochemical, lipophilicity, medicinal chemistry, drug-likeness, absorption, water solubility, distribution, metabolism, pharmacokinetics, and excretion) and PASS prediction. To validate the wet lab results, both Gram-positive and Gram-negative bacterial strains were used. Docking studies demonstrated that all ligands efficiently bind to all seven PBPs (PBP1a, PBP2a, PBP3, PBP4, PBP5, and PBP6) with docking score ranged from − 4.2 to − 6.9 (vina score). The interaction investigations reveal that the PBP-Ligand complexes have hydrogen and hydrophobic contacts. Additionally, in order to confirm the docking results and provide clarification on certain aspects of the thermodynamic and dynamic properties of the two most promising ligand-pocket complexes from docking studies (Humulene oxide and Spathulenol), molecular dynamics (MD) simulations were performed. The in-silico ADMET study showed that all ligand molecules were non-toxic and had good absorption properties. Both REO and TEO were able to inhibit both Gram-positive and Gram-negative bacterial strains with zone of inhibition values ranged from 0.2 cm to 1.3 cm. Based on in silico and in vitro validation studies, it was proved that due to the richness of phytocompounds having therapeutic potential, tea tree and rosemary essential oils may be effective antibacterial agents in food and pharmaceutical companies.