Identification and molecular mechanisms of novel antioxidant peptides from Manila clam hydrolysate: Caenorhabditis elegans model, molecular simulations, and quantum chemistry

The objective of the study was to identify antioxidant peptides from Manila clam hydrolysates. Results demonstrated that the enzymatic hydrolysate of Manila clam (MW < 1 kDa) (RPPH-1) exhibited significant in vitro antioxidant activity and in vivo Anti-aging effects. Specifically, the activities of Glutathione Peroxidase (GSH-Px) in the 1.5 mg/mL RPPH-1 dosage group increased by 1.44-fold compared with the control group. The lifespan of Caenorhabditis elegans was prolonged. Among the 19 identified peptides, FDCSQFKPEE (FE10) formed van der Waals and hydrophobic interactions with Keap1 via residues Leu557, Leu365, Ile559, Tyr334, and Phe577, indicating stability of the FE10-Keap1 complex. Quantum chemical analysis revealed that the active site of FE10 was Phe N₁₆H₁₀₃ and exhibited the lowest energy difference between the LUMO and HOMO. The radical scavenging activities of DPPH and ABTS were 62.77 % and 98.15 %, respectively. The present results indicated that the Manila clam hydrolysates exhibited potent antioxidant activities.

Antioxidant peptide; Caenorhabditis elegans; Manila clam; Molecular simulation; Quantum chemistry.