Identification, structure-activity relationship and in silico molecular docking analyses of five novel angiotensin I-converting enzyme (ACE)-inhibitory peptides from stone fish (Actinopyga lecanora) hydrolysates

Abstract

Stone fish is an under-utilized sea cucumber with many health benefits. Hydrolysates with strong ACE-inhibitory effects were generated from stone fish protein under the optimum conditions of hydrolysis using bromelain and fractionated based on hydrophobicity and isoelectric properties of the constituent peptides. Five novel peptide sequences with molecular weight (mw) < 1000 daltons (Da) were identified using LC-MS/MS. The peptides including Ala-Leu-Gly-Pro-Gln-Phe-Tyr (794.44 Da), Lys-Val-Pro-Pro-Lys-Ala (638.88 Da), Leu-Ala-Pro-Pro-Thr-Met (628.85 Da), Glu-Val-Leu-Ile-Gln (600.77 Da) and Glu-His-Pro-Val-Leu (593.74 Da) were evaluated for ACE-inhibitory activity and showed IC 50 values of 0.012 mM, 0.980 mM, 1.310 mM, 1.440 mM and 1.680 mM, respectively. The ACE-inhibitory effects of the peptides were further verified using molecular docking study. The docking results demonstrated that the peptides exhibit their effect mainly via hydrogen and electrostatic bond interactions with ACE. These findings provide evidence about stone fish as a valuable source of raw materials for the manufacture of antihypertensive peptides that can be incorporated to enhance therapeutic relevance and commercial significance of formulated functional foods.

Two novel potent ACEI peptides isolated from Pinctada fucata meat hydrolysates using in silico analysis: identification, screening and inhibitory mechanisms

“…Furthermore, some studies have indicated that peptides with HAAs at the C-and N-terminals might enhance ACEI activity. 31,32 In this study, the IC 50 value of the tetrapeptide LPYY was determined to be 116.26 mM. The inhibitory activity of LPYY may be attributed to its high ratio of HAA residues as well as its hydrophobic-hydrophilic-hydrophobic structure in the peptide sequencethe highly HAAs Leu and Tyr are located at the Nand C-terminals, respectively, whereas the hydrophilic amino acid Pro occupies the second position.…”

Investigation of Chlorella pyrenoidosa Protein as a Source of Novel Angiotensin I-Converting Enzyme (ACE) and Dipeptidyl Peptidase-IV (DPP-IV) Inhibitory Peptides

“…Among commonly used in silico methods, molecular docking permits researchers to evaluate the interaction between peptides and complex proteins, in order to predict the binding free energy values and the putative binding modes [ 41 ]. A similar work-flow has been applied for discovering novel ACE inhibitory peptides from stone fish protein hydrolysates [ 42 ]. Besides the molecular docking study, here also MD simulations were performed in order to evaluate the stability of the complex during a specified simulation time, improving greatly the accuracy of the predictions.…”

Angiotensin Converting Enzyme (ACE)-Peptide Interactions: Inhibition Kinetics, In Silico Molecular Docking and Stability Study of Three Novel Peptides Generated from Palm Kernel Cake Proteins

“…Docking is a computer-based method that predicts the affinity and binding conformation of a small molecule ligand (an inhibitor) to the appropriate target binding site (an enzyme) in order to determine and evaluate the hydrogen bond, hydrophobic interaction, electrostatic interactions, Van der Waals interaction force and total energy between peptide and ACE [14,15]. Recently, in silico molecular docking has been used to study the interaction between inhibitory peptides and ACE in pistachio hydrolysate [15], Salmo salar [16], milk protein [17], hemp seed [12] and stone fish hydrolysates [18].…”