Structural Characterization and Biological Activity of Oligopeptides from Isochrysis zhanjiangensis: Based on Quantum Mechanics, Molecular Docking and in Vitro Experiments

DAPTMGY (DTY) is an oligopeptide derived from marine microalgae with proven potential to combat oxidative stress in previous research. The composition, ordering, and active sites of amino acids play a key role in activity studies and are also the research trends in recent years. As an oligopeptide with a molecular weight of less than 1000 Da, DTY is of great significance to explore the active site and structure-activity relationship. This study used quantum mechanics to optimize DTY's structure and predict the active site through molecular orbits, energy, and charge. In addition, an LPS-treated HUVEC cell was established as an oxidative-stress model. DTY could reduce mitochondrial oxidative stress and inhibit ROS production by enhancing the antioxidant enzymes SOD, GPX, and HO-1. Moreover, it was confirmed to inhibit inflammation and apoptosis through the NF-kappa B and MAPK signaling pathways. Lastly, the correlation of the oligopeptide DTY's active site and antioxidative-stress activity was verified by molecular docking, showing that hydrogen bonding is the main force, which was also the main factor for antioxidant activity.