Pharmacophore-based virtual screening, molecular docking, MD simulation, MM-GBSA energy calculation and DFT analysis for the in silico discovery of a SaFtsZ inhibitor

Abstract

The rapid emergence of antimicrobial resistance demands the discovery of new antibacterial targets and inhibitors. Staphylococcus aureus filamenting temperature-sensitive protein (SaFtsZ), an essential cytoskeletal protein involved in bacterial cytokinesis and Z-ring formation, has gained attention as a promising target for antibacterial drug discovery. In the present study, an integrated computational strategy involving pharmacophore mapping, molecular docking, molecular dynamics (MD) simulations, and density functional theory (DFT) analysis was employed to identify potential SaFtsZ inhibitors. Initially, large compound library was screened from the Pharmit database using a structure-based pharmacophore model to identify molecules with key interaction features required for SaFtsZ inhibition. The selected 200 candidates were further evaluated through molecular docking to determine their binding affinity and interaction pattern within the active site of SaFtsZ. Among the screened molecules, compound 15 (CID 135468497) exhibited the highest binding affinity with a docking score of −10.8 kcal mol−1. Subsequent MD simulation confirmed the stability of the protein–ligand complex, while DFT analysis provided insights into the electronic characteristics and reactivity of compound 15. These findings highlight compound 15 as a computationally predicted scaffold for the development of SaFtsZ-targeted antibacterial agents. However, experimental validation is required to confirm the computational results.