Interaction mechanisms of ACE inhibitory peptides: molecular docking and molecular dynamics simulation studies on five wheat gluten derived peptides

The angiotensin I-converting enzyme (ACE) inhibitory activity of five wheat gluten-derived peptides Ala-Pro-Ser-Tyr (APSY), Leu-Val-Ser (LVS), Leu-Tyr (LY), Arg-Gly-Gly-Tyr (RGGY), and Tyr-Gln (YQ) was investigated, demonstrating excellent inhibitory activity against ACE. Among these peptides, LY exhibited the strongest inhibitory activity. Molecular docking analyses revealed that these peptides inhibited ACE by forming multiple bonds and engaging in hydrophobic interactions with residues in the active site pockets, particularly the S1 (TYR-523, ALA-354, GLU-384) and S2 (HIS-353, HIS-513, GLN-281, TYR-520) pockets. Molecular dynamics simulations further confirmed the formation of stable complexes between the peptides and ACE. The RMSD, SASA, RMSF, Rg, and FEL graphs provided insights into the changes in stability, flexibility, and compactness of the ACE-peptide complexes. The binding affinity between the peptides and ACE was primarily influenced by electrostatic and van der Waals interactions, as well as nonpolar solvation energy, indicating strong binding ability. These findings elucidated the molecular mechanism by which these ACE inhibitory peptides interact with the active pockets of ACE, offering a theoretical basis for the development of hypertension treatments.