Prediction of ACE-I Inhibitory Peptides Derived from Chickpea (Cicer arietinum L.): In Silico Assessments Using Simulated Enzymatic Hydrolysis, Molecular Docking and ADMET Evaluation

Abstract

Chickpea (Cicer arietinum L.) peptides have shown in vitro potential to inhibit the angiotensin I-converting enzyme (ACE-I). However, the potential molecular interactions between chickpea peptides (CP) and ACE-I as well as their ADMET (absorption/distribution/metabolism/excretion/toxicity) characteristics remain unknown. Thus, our aim was to study the in silico interactions of CP with ACE-I and the CP ADMET characteristics. Legumin and provicilin sequences were submitted to in silico analysis to search for ACE-I inhibitory peptides. Simulated enzymatic hydrolysis was performed using the BIOPEP-UWM database, and the ACE-I inhibitory peptides generated (EC50 ≤ 200 μM) were selected to perform molecular docking and ADMET analysis. After hydrolysis, 59 out of 381 peptides with ACE-I inhibitory potential were released. Based on A and B parameters, the legumin peptides showed better ACE-I inhibitory potential than the provicilin ones. CP mainly interact with residues from pocket S1 (Ala354/Glu384) and S2 (His353/His513) through hydrogen bonds (distances < 3.0 Å) and hydrophobic interactions (binding energy from −5.7 to −9.2 kcal/mol). Through ADMET analysis, CP showed optimal values for inhibiting ACE-I in vivo. ACE-I inhibitory peptides from legumin and provicilin can bind strongly and tightly to the active site of ACE-I. Further studies to evaluate in vivo the antihypertensive effects of CP are warranted.

RETRACTED: In-silico modelling studies of 5-benzyl-4-thiazolinone derivatives as influenza neuraminidase inhibitors via 2D-QSAR, 3D-QSAR, molecular docking, and ADMET predictions

“…From Lipinski's table of the lead molecules in the data set, the Log P scores of the molecules are relatively close to 3 log mol/L (optimal limit) except for molecule 17 which is slightly above the optimal limit (0 < Log P < 3). This implies that the molecules have low aqueous solubility and good oral bioavailability (Adianingsih et al, 2022;Ar amburo-G alvez et al, 2022). The Log P also gives information on the cellular membrane permeability and hydrophobic binding to macromolecules such as the target receptors, plasma proteins, metabolizing enzymes, or transporters (Dowdy et al, 2022).…”

Extrusion Improves the Antihypertensive Potential of a Kabuli Chickpea (Cicer arietinum L.) Protein Hydrolysate

“…The findings have implications for producing ingredients for functional foods that could help to prevent hypertension or serve as an adjunct in the treatment of this non-communicable disease. Further studies directed to identifying the peptide profile of extruded and unextruded chickpea protein hydrolysates and their analysis under an in silico approach proposed previously (simulated enzymatic hydrolysis and ADMET prediction followed by molecular docking [ 9 ]) are warranted.…”

“…Chickpea is a legume or pulse that contains around 20–22% of highly bioavailable protein with a balanced amino acid profile [ 8 ]. In silico and in vitro studies have highlighted that chickpea hydrolysates or peptides obtained with gastrointestinal or non-gastrointestinal enzymes—such as pepsin, trypsin, alcalase, and flavourzyme—can inhibit ACE-I [ 9 , 10 , 11 , 12 ], but their antihypertensive potentials have not been evaluated yet. Notably, globulins account for 60–80% of the extractable protein fraction from chickpeas, but the globular protein structure might be a limiting factor for in vitro proteolysis or even digestion in mammals [ 13 ].…”

Computational modelling studies of some 1,3-thiazine derivatives as anti-influenza inhibitors targeting H1N1 neuraminidase via 2D-QSAR, 3D-QSAR, molecular docking, and ADMET predictions

“…The four lead compounds which have passed the Lipinski rule of five (Table 10) were further assessed with other druglikeness filter rules such as the Ghose filter rule, Veber's From Lipinski's table of the lead compounds in the dataset, the Log P scores of the compounds are relatively high close to 3 log mol/L which is the optimal limit (0 < log P < 3). This implies that the compounds have low aqueous solubility and good oral bioavailability [47,48]. The Log P also gives information on the cellular membrane permeability and hydrophobic binding to macromolecules such as the target receptors, plasma proteins, metabolizing enzymes, or transporters [49].…”