Dataset Information

Physicochemical characterisation, molecular docking, and drug-likeness evaluation of hypotensive peptides encrypted in flaxseed proteome.

ABSTRACT: In this study, hypotensive peptides derived from mature flaxseed protein sequences were predicted in silico using BIOPEP-UWM with nine proteases, three each from digestive, plant and microbial sources. The physicochemical properties of 2256 ACE-inhibitory peptides and 267 renin-inhibitory peptides (including seven (7) peptides with dual inhibitory activities against both ACE and renin enzymes) were assessed in silico using the 'Peptides' package of R. The hypotensive peptides showed relatively low molecular weight (mol. wt.) range (132 = mol. wt. ? 442 Da); broad range of isoelectric point (3.61 = pI ? 12.50); both high (>2) and low (?2) Boman indices, and a variety of hydrophobicity indices (hydrophilic, hydrophobic and amphipathic properties). Following this, the seven peptides with dual ACE and renin inhibitory activities were selected for molecular docking with the respective enzyme receptors. The binding energies of the seven hypotensive peptides with ACE and renin respectively ranged from -36.82 to -25.94 kJ/mol, and -33.05 to -27.61 kJ/mol; and compared well with values recorded for inhibitor drugs, captopril (-26.78 kJ/mol) and aliskiren (-34.73 kJ/mol). The seven peptides inhibited ACE through hydrogen bonds, electrostatic and hydrophobic interactions; and renin, mainly through hydrogen bonds and hydrophobic interactions. In silico prediction of adsorption, digestion, metabolism, excretion and toxicity (ADME/Tox) profile based on physicochemical properties and Lipinski's rule-of-five showed that the peptides were non-toxic and had desirable drug-like properties (flexibility, lipophilicity, molecular weight, gastrointestinal absorption, and bioavailability). This study provides insight into the molecular interactions of hypotensive peptides with their physiological targets, and the potential to develop the bioactive peptides from flaxseed proteins.

SUBMITTER: Ji D

PROVIDER: S-EPMC7473365 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Physicochemical characterisation, molecular docking, and drug-likeness evaluation of hypotensive peptides encrypted in flaxseed proteome.

Ji Dawei D Xu Min M Udenigwe Chibuike C CC Agyei Dominic D

Current research in food science 20200314

In this study, hypotensive peptides derived from mature flaxseed protein sequences were predicted in silico using BIOPEP-UWM with nine proteases, three each from digestive, plant and microbial sources. The physicochemical properties of 2256 ACE-inhibitory peptides and 267 renin-inhibitory peptides (including seven (7) peptides with dual inhibitory activities against both ACE and renin enzymes) were assessed in silico using the 'Peptides' package of R. The hypotensive peptide ...[more]

PMID: 32914119

Similar Datasets

Project description:Computer aided toxicity and pharmacokinetic prediction studies attracted the attention of pharmaceutical industries as an alternative means to predict potential drug candidates. In the present study, in-silico pharmacokinetic properties (ADME), drug-likeness, toxicity profiles of sixteen antidiabetic flavonoids that have ideal bidentate chelating sites for metal ion coordination were examined using SwissADME, Pro Tox II, vNN and ADMETlab web tools. Density functional theory (DFT) calculations were also employed to calculate quantum chemical descriptors of the compounds. Molecular docking studies against human alpha amylase were also conducted. The results were compared with the control drugs, metformin and acarbose. The drug-likeness prediction results showed that all flavonoids, except myricetin, were found to obey Lipinski's rule of five for their drug like molecular nature. Pharmacokinetically, chrysin, wogonin, genistein, baicalein, and apigenin showed best absorption profile with human intestinal absorption (HIA) value of ≥ 30%, compared to the other flavonoids. Baicalein, butein, ellagic acid, eriodyctiol, Fisetin and quercetin were predicted to show carcinogenicity. The flavonoid derivatives considered in this study are predicted to be suitable molecules for CYP3A probes, except eriodyctiol which interacts with P-glycoprotein (p-gp). The toxicological endpoints prediction analysis showed that the median lethal dose (LD50) values range from 159-3919 mg/Kg, of which baicalein and quercetin are found to be mutagenic whereas butein is found to be the only immunotoxin. Molecular docking studies showed that the significant interaction (-7.5 to -8.3 kcal/mol) of the studied molecules in the binding pocket of the α-amylase protein relative to the control metformin with the crucial amino acids Asp 197, Glu 233, Asp 197, Glu 233, Trp 59, Tyr 62, His 101, Leu 162, Arg 195, His 299 and Leu 165. Chrysin was predicted to be a ligand with high absorption and lipophilicity with 84.6% absorption compared to metformin (78.3%). Moreover, quantum chemical, ADMET, drug-likeness and molecular docking profiles predicted that chrysin is a good bidentate ligand.

Dataset Information

Physicochemical characterisation, molecular docking, and drug-likeness evaluation of hypotensive peptides encrypted in flaxseed proteome.

Publications

Physicochemical characterisation, molecular docking, and drug-likeness evaluation of hypotensive peptides encrypted in flaxseed proteome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets