In silico analysis and antihypertensive effect of ACE-inhibitory peptides from smooth-hound viscera protein hydrolysate: Enzyme-peptide interaction study using molecular docking simulation

Smooth-hound viscera proteins were enzymatically hydrolyzed, using Esperase, and the resulting hydrolysate was fractionated by ultrafiltration through four membranes with decreasing molecular weight (MW) cut-offs. Five fractions were obtained, FI (> 50 kDa), FII (5-50 kDa), FIII (3-5 kDa), FIV (1-3 kDa) and FV (< 1 kDa). Their RP-HPLC peptide profile, amino acid compositions, and ACE-inhibitory activity were investigated and compared to the non-fractionated hydrolysate. Data showed that fractions with low MW peptides contained the highest amounts of hydrophobic amino acids (39.63 and 41.68% in FIV and FV, respectively). In addition, FIV and FV exhibited the strongest ACE-inhibitory activity with respective IC50 of 101.61 and 92.75 mu g/ml. Moreover, they showed interesting blood pressure-lowering results in hypertensive rats after 4 h of oral administration (200 mg/kg body weight). Both fractions were then fractionated by RP-HPLC and eluted peptides were analyzed by nanoLC-MS/MS. The molecular docking study of IAGPPGSAGPAG, VVPFEGAV, PLPKRE, and PTVPKRPSPT showed that peptides were able to bind ACE through a complex of hydrophobic, hydrogen bonds, van der Waals and electrostatic interactions, as well as to interact with the three residues coordinating with Zn2+. Hence, this study provides a useful bioprocess for the use of smooth-hound byproducts as a natural source of hypotensive agents.