Identification and In Silico Selection of Novel Antioxidant Peptides from Asian Swamp Eel Bone: Quantum Chemical Calculations, Molecular Docking, and Zebrafish Model Validation

Fourteen novel antioxidant peptides were screened from the enzymatic hydrolysates of Asian swamp eel bone (ASEB) through an in silico analysis. Their ABTS and ORAC radical scavenging capacities were 1.70–4.29-fold and 2.79–5.90-fold higher than those of Trolox, respectively. Additionally, two novel peptide sequences (NVGW and WALN) were identified. Quantum chemical calculations combined with active–-site methylation experiments demonstrated that hydrogen atoms on tryptophan’s indole nitrogen, tyrosine’s phenolic hydroxyl, and arginine’s guanidinium group play crucial roles in enhancing ABTS and ORAC activities. Molecular docking further showed stable binding of ASEB peptides to myeloperoxidase (MPO) through hydrogen bonds and electrostatic interactions. Further studies indicated that ASEB alleviated oxidative stress in zebrafish by effectively reducing ROS accumulation, restoring redox homeostasis, and modulating the expression of Keap1–Nrf2 pathway-related antioxidant genes. These results enhance our understanding of the antioxidant properties of ASEB-derived peptides and support the high-value utilization of animal byproducts.