Abstract: The C-domain selective angiotensin-converting enzyme (ACE) inhibitory activities of food-derived dipeptides, including Ile-Trp (IW) and Val-Trp (VW), were recently verified by experiments. However, their interaction modes with the C-domain and N-domain of ACE and the molecular mechanism remain unclear. In the present study, flexible molecule docking technology was used to elucidate the active sites, interaction energy and intermolecular force types between the peptides and ACE. The results demonstrated that hydrogen bond, hydrophilic, hydrophobic and electrostatic interactions, and coordinate bond existed between the active pockets of the C-domain and IW and VW. The interaction of the N-domain with the peptides was similar to that of the C-domain, which had fewer hydrogen bonds and no electrostatic interactions. By calculating the binding energy difference between the two domains, we could seek the theoretical support for the different inhibitory potency of IW and VW. The above information will be helpful for the development of C-domain selective ACE inhibitory peptides.

Key words: ACE, C-domain selective inhibitory peptides, flexible docking, interaction mode