In silico assessment of barnyard millet and blue pea derived bioactive peptides against Salmonella enterica Serovar Typhi and Clostridioides difficile

Natural food derived bioactive peptides have been increasingly recognised for their natural origin, improved biocompatibility, and potent antimicrobial activities. In the current study, a comprehensive computational framework has been employed to evaluate the potency of bioactive peptides against major GI causing pathogens such as Salmonella Typhi and Clostridioides difficile . A total of 519 candidate peptides were screened based on antimicrobial properties, toxicities, anti-inflammatory activity and allergenicity, which yielded two promising peptides (P1: biopep02815 and P2: biopep02950). Molecular docking against key pathogenic targets, TcdA, TcdB and OmpF revealed strong binding affinity with ClusPro docking scores ranging from − 706 to − 920. Subsequent molecular dynamics simulations and binding free energy analyses confirmed the structural stability and favourable interaction energies of the protein-peptide complexes that are primarily driven by van der Waals and electrostatic energy components. The present findings of the study underscore the antimicrobial potential of the food derived bioactive peptides against prevalent GI pathogens, paving their way to future experimental and clinical investigations.