Investigating the potential phytochemical inhibitors against PvrA protein of Pseudomonas aeruginosa using In Silico approaches

The opportunistic, gram-negative bacterium Pseudomonas aeruginosa is a serious threat to human health, especially in individuals with weakened immune systems. It is well known to cause serious infections in the urinary system, burns, wounds, and airways (i.e., pneumonia). It also plays a significant role in the development of hospital-acquired infections. This is a serious concern because of its capacity to build biofilms and withstand medication. P. aeruginosa uses alternate energy sources such as nitrate, pyruvate, and arginine to survive in a variety of settings, including low oxygen levels. Pyocyanin, rhamnolipids, and exotoxins are among the components that contribute to its pathogenicity, which are controlled by quorum-sensing systems (Las, Rhl, and PQS). Pseudomonas Virulence Regulator A (PvrA) is an important pathogenic protein of P. aeruginosa . This study focused on identifying the key potential phytochemical inhibitor from the screened ligands of the IMMPAT library. This protein is essential for toxin synthesis, biofilm development, and host cell destruction. The active sites of the chosen proteins were identified using COACH, PRANK web, and literature, and their structural integrity was confirmed using ERRAT, PROCHECK and VERIFY 3d. Ligands were selected for drug development from a phytochemical library after evaluation of their ADMET characteristics. Molecular docking of PvrA protein using AutoDock 1.5.7 with a flexible ligand and a grid box of 60 × 60 × 60 points centered at X = 36.954, Y= 1.85, Z = 14.034 identified Aristololactam-glucoside as the top ligand with binding energy of −9.2 kcal/mol, with interactions visualized via Discovery Studio to confirm stable binding and key active site engagement. MD simulations identified the top ligand as a potential inhibitor. The stability of the protein–ligand complex was confirmed through RMSD, RMSF, Rg, and total hydrogen bond analyses.