Virtual screening and molecular docking for exploring ACE inhibitory peptides in Larimichthys crocea nebulin protein.

Larimichthys crocea nebulin protein was selected to explore novel angiotensin-converting enzyme (ACE) inhibitory peptides. After in silico gastrointestinal proteolysis using pepsin, trypsin and chymotrypsin, several tripeptides were obtained. Then, the cytotoxicity, solubility, bioactivity probability, and adsorption, distribution, metabolism and excretion (ADME) properties of the tripeptides were predicted using online prediction tools. Molecular docking was performed to screen the tightly bound peptides to investigate the interactions between ACE and the novel tripeptides. Finally, potent ACE inhibitory tripeptides were used to explore the active pharmacophores. These results suggested that the tripeptide HGR (His-Gly-Arg) exhibited effective ACE inhibitory activity, with an IC₅₀ value of 106 ± 1.35 µM. The HGRACE complex is stabilised by 14 hydrogen bonds, one attractive charge, and one pi-alkyl interaction. In addition, HGR made contact with the major residues of ACE, i.e., His353, Glu384, Ala354, His513, Tyr523, and Lys511. Furthermore, hydrogen bond acceptors and hydrophobicity are inevitably the most important active features of ACE inhibitory tripeptides, especially hydrogen bond acceptors. [ABSTRACT FROM AUTHOR]