Leveraging molecular dynamics, physicochemical, and structural analysis to explore OMP33-36 protein as a drug target...

The Acinetobacter baumannii is a member of the "ESKAPE" bacteria responsible for many serious multidrug-resistant (MDR) illnesses. This bacteria swiftly adapts to environmental cues leading to the emergence of multidrug-resistant variants, particularly in hospital/medical settings. In this work, we have demonstrated the outer membrane protein 33-36 (Omp33-36) porin as a potential therapeutic target in A. baumannii and the regulatory potential of phytocompounds using an in-silico drug screening approach. Omp33-36 protein receptor was retrieved from the protein data bank and characterized as a receptor protein. The possible compounds (ligands) from three plants namely Andrographis paniculata, Cascabela thevetia, and Prosopis cineraria, were evaluated for their potential against bacterial infections based on prior investigations and selected for further analysis. Initially, seventy potential phytocompounds were identified and retrieved from IMPPAT database, followed by Physio-chemical characterizations and toxicity assessment using swissADME and ProTox server respectively. 15 compounds have shown significant drug-likeliness and were implemented for their interaction analysis with Omp33-36 using Autodock Vina. The docking study presented seven compounds with the best binding affinities, ranging from -7.2 kcal/mol to -7.9 kcal/mol and further, based on the potential of these compounds, 4 phytocompounds were introduced for molecular dynamic simulation for 200ns. During MD simulation, compounds Prosogerin, Quercitin and Tamarixetin have shown a substantial affinity for the Omp33-36 protein and binding energy ranging from -18 to -33 kcal/mol. Overall, the analysis depicted the two compounds, Quercitin and Tamarixetin, with the most consistent interactions and indicated promise as drug leads in regulating A. baumannii infection. However, in-vitro and in-vivo experimental validation are required to propose the selected phytomolecules as a therapeutic lead against A. baumannii.