In Silico Design and Molecular Docking of Esp C-terminal Domain Inhibitors in Enterococcus faecalis

Enterococcus faecalis, a gram-positive bacterium linked to hospital-acquired infections, exhibits strong biofilm formation mediated by the Enterococcus Surface Protein (Esp), contributing to its persistence and antibiotic resistance. This study computationally evaluated small-molecule inhibitors targeting the Esp C-terminal adhesion domain. The Esp structure was prepared using AutoDock Tools, and ligands were optimized via Open Babel and docked with AutoDock 4.2. Top hits were filtered with AutoDock Vina, and binding interactions were visualized using MGLTools. SwissADME analysis assessed physicochemical and pharmacokinetic profiles. Baicalein, curcumin, and pyridazinone displayed high binding affinity (up to −9.63 kcal/mol), with baicalein analogues achieving −10.1 kcal/mol. The lead compound demonstrated drug-like properties, indicating strong potential as a therapeutic candidate.