Identifying therapeutic antibacterial peptides against Vibrio cholerae to inhibit the function of Na(+)-translocating NADH-quinone reductase

Vibrio cholerae is the bacteria responsible for cholera, which is a significant threat to many nations. Curing and treating this infection requires identification of the critical protein and development of a drug to inhibit its function. In this context, Na(+)-translocating NADH-quinone reductase was considered a potential therapeutic target. A library of antibacterial peptides with residue lengths of 50 was screened using a docking method, and the five most potent peptides were selected on the basis of a weighted score derived from solvent accessible surface area and docking score. To investigate the stability of the protein-peptide complex, a 100-ns molecular dynamics simulation was performed. These peptides targeted the native dimeric binding interface of Na(+)-transporting NADH-quinone reductase. This study evaluated the binding affinity and conformational stability of these peptides with the protein using different post-simulation metrics. A peptide, CCL28, exhibited steady RMSD characteristics; nonetheless, it modified the docked conformation but stabilized in the new conformation. This peptide also demonstrated the best performance in addressing the protein's native binding interface. It demonstrated a binding free energy of -120 kcal/mol with the protein. Principal component analysis (PCA) revealed that the first PC had the lowest conformational variation and the greatest coverage. Eventually, these peptides were also evaluated using steered molecular dynamics, and it was discovered that CCL28 had a greater maximum force than the other five peptides, at 1139.08 kJ/mol/nm. Targeting the native binding interface, we present a CCL28 peptide with a strong potential to block the biological activity of Vibrio cholerae's Na(+)-translocating NADH-quinone reductase.