The peptide deformylase protein (PDF) has emerged as a promising target for the discovery of novel antibiotics with a novel mechanism of action. The current investigation was aimed at identifying potential inhibitor of PDF by using structure-based pharmacophore modelling. The pharmacophore hypothesis consisted of one hydrophobic, one negative ionizable, and one hydrogen bond donor features which were built using the structure of cognate ligand of PDF (BB2). Further, the pharmacophore model was validated and used to screen hit molecule against Indonesian Medicinal Plant Database and retrieved 32 hit molecules. All hit molecules were docked to PDF and four best molecules were subjected for 50-ns molecular dynamics (MD) simulation. MD simulation confirmed the docked poses of ligand as indicated by the RMSD and RMSF values. Prediction of affinities employing Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) method revealed that quercetin 3-(6''-malonylneohesperidoside) had a comparable affinity with that of BB2, which indicated its potential as a novel herbal-based PDF inhibitor.
- Molecular dynamics simulation
- Peptide deformylase protein (PDF)
- Pharmacophore modeling
- Virtual screening