ABSTRACT
Understanding the dual inhibition mechanism of food derivative peptides targeting the enzymes (Renin and Angiotensin Converting enzyme) in the Renin Angiotensin System. Two peptides RALP and WYT were reported to possess antihypertensive activity targeting both renin and ACE, and we have used molecular docking and molecular dynamics simulation, in order to understand the underlying mechanism. The selected peptides (RALP and WYT) from the series of peptides reported were docked to renin and ACE and two binding modes were selected based on the binding energy, interaction pattern and clusters of docking simulation. The enzyme-peptide complexes for renin and ACE (Renin/RALP1,2; ACE/RALP1,2; Renin/WYT1,2 and ACE/WYT1,2) were subjected to molecular dynamics simulation. Our results identified that the peptides inhibiting renin, tends to move out of the binding pockets (S1' S2') which is critical for potent binding and occupies the less important pockets (S4 and S3). This could possibly be the reason for its low potency. Whereas, the same peptides targeting ACE, tends to be intact in the pocket because of the metal ion coordination and there is an ample room to improve on its efficacy. Our results further pave way for the biochemist, medicinal chemist to design dual peptides targeting the RAS effectively. Communicated by Ramaswamy H. Sarma.
