Studies on molecular mechanism between ACE and inhibitory peptides in different bioactivities by 3D-QSAR and MD simulations

3D-QSAR, molecular docking and molecular dynamics (MD) simulations were performed to investigate the mechanism of ACE-inhibitory (ACEi) peptides with tryptophan C-terminal in aqueous solutions. In this work, COMFA (Q(2) = 0.85, R-2 = 0.993) and COMSIA (Q(2) = 0.706, R-2 = 0.997) models of di- and tri-peptides were established. Novel tripeptides were predicted by the 3D-QSAR models. Different conformations and interactions between VKW with high activity and GTW with low activity were compared by MD simulation. The results revealed VKW had stronger electrostatic interaction and binding affinity with key residues of ACE. ACE-VKW complex performed more stable than ACE-GTW. Thus, VKW showed a higher activity. Moreover, ACEi tripeptides with Trp C-terminal potentiate the combination with Zn of ACE active pockets. (C) 2020 Elsevier B.V. All rights reserved.