screening of bioactive phytopeptides for novel anti-ageing therapeutics.

A metabolic network of energy-sensing molecular pathways drives the biological ageing process. Regulating certain network elements can help decelerate the ageing process and ameliorate ageing associated disorders. Bioactive phytopeptides are a prospective avenue for anti-ageing therapeutics and rejuvenation biotechnology. The present study investigates the potential of therapeutic plant peptides against cellular senescence by targeting three key proteins in the ageing network - target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). This investigation screened a library of reported bioactive peptides using standard cheminformatic methods including ADMET, molecular docking, molecular dynamics simulation and molecular mechanics calculation. The retrieved simulation data predict 25 diverse phytopeptides as potential safe and drug-like anti-ageing biologics with half-lives >20 h and bioavailability scores >0.40. The best docked peptide, Cycloleonuripeptide B, exhibited strong binding affinity and stable complex formation with mTOR (-17.5 kCal/mol), SIRT1 (-28.54 kCal/mol) and two active sites in AMPK (-41.8 kCal/mol; -36.0 kCal/mol) during molecular dynamics simulations. The computational study acts as a foundation for future laboratory and clinical research into the potential of repurposing therapeutic phytopeptides against cellular senescence and associated pathophysiology. Communicated by Ramaswamy H. Sarma.