Angiotensin I-Converting Enzyme (ACE) Inhibition Mechanism of Novel Peptides from Velvet Bean: An In Silico Study

Abstract

Velvet bean (Mucuna pruriens) peptides are potential ACE inhibitors. This study aimed to identify peptides from velvet bean protein hydrolysate which contribute significantly to ACE inhibitory activity and predict its inhibition mechanism. LC-MS analysis was conducted to identify peptide sequences. Molecular docking was performed to screen for potential ACE inhibitory peptides. Based on the resulting docking scores, four peptides (P1 - EQPRPYPYPRP, P2 - FCRFGVLKV, P3 - QTDEYGNPVHRS, P4 - QTDEYGNPVHR) were selected. Binding mode analysis showed that ACE inhibition by the novel peptides was a combination of competitive and noncompetitive. P1 and P3 were hypothesized to be competitive inhibitors which were able to coordinate with the enzyme’s cofactor (i.e., Zn2+), whereas P2 and P4 were hypothesized to be noncompetitive inhibitors as they were only able to form hydrophobic networks with the binding channels and were unable to coordinate with Zn2+. Furthermore, molecular dynamics simulations demonstrated slight changes in the conformation of the enzyme as a result of peptide binding, confirming the novel velvet bean-based peptides as ACE inhibitors.