Antimicrobial activity of Geranyl acetate against cell wall synthesis proteins of and using molecular docking and simulation.

Incidences of Methicillin-Resistant and Multi-Drug Resistant causing skin and soft tissue infections are becoming more prevalent due to repeated mutations and changes in the environment. a well-known Indian herbal medicinal plant, is shown to have antioxidant, antibacterial, and anti-inflammatory activity. This comparative study focuses on the molecular docking (PyRx v0.9.8) of ligand binding domains of WbpE Aminotransferase involved in O-antigen assembly in (3NU7) and Beta-Lactamase found in (1BLC) with selected phytocompounds of along with a known binder and a clinical reference drug. This was followed by molecular dynamics simulation studies (GROMACS v2019.4) for the docked complexes (with Geranyl acetate) with the best binding affinities (-23.4304 kJ/mol with Beta-Lactamase and -28.4512 kJ/mol with WbpE Aminotransferase) and maximum hydrogen bonds. Molecular dynamics simulation studies for both the proteins demonstrated that the complex with Geranyl acetate showed stability comparable to the complex with reference drug observed Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and H-bond analyses. Changes in the secondary structural elements indicated that Geranyl acetate could possibly cause improper functioning of WbpE Aminotransferase leading to disrupted cell wall formation. Further, MM/PBSA analyses showed significant binding affinity of Geranyl acetate with WbpE Aminotransferase and Beta-Lactamase. This study aims to provide rationale for further studies of as an antimicrobial, and to contextualise the results in the current scenario of growing antimicrobial resistance. HIGHLIGHTSPhytoconstituents present in show significant binding affinity to the proteins in and Geranyl acetate exhibited the highest binding affinity with WbpE Aminotransferase involved in O-antigen assembly in (PDB ID:3NU7) and Beta-Lactamase found in (PDB ID: 1BLC)Molecular dynamics simulation analyses show that the phytoconstituent, Geranyl acetate has an effect similar to the clinical reference drug, thus exhibiting potential antibacterial activity.Communicated by Ramaswamy H. Sarma.