{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T22:07:39Z","timestamp":1783030059340,"version":"3.54.6"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Supercomputing Center\u2014IPICYT","award":["TKII-AMVL001"],"award-info":[{"award-number":["TKII-AMVL001"]}]},{"name":"National Supercomputing Center\u2014IPICYT","award":["DGTIC-347"],"award-info":[{"award-number":["DGTIC-347"]}]},{"name":"National Supercomputing Center\u2014IPICYT","award":["1019794"],"award-info":[{"award-number":["1019794"]}]},{"name":"LANCAD","award":["TKII-AMVL001"],"award-info":[{"award-number":["TKII-AMVL001"]}]},{"name":"LANCAD","award":["DGTIC-347"],"award-info":[{"award-number":["DGTIC-347"]}]},{"name":"LANCAD","award":["1019794"],"award-info":[{"award-number":["1019794"]}]},{"name":"USDA National Institute of Food and Agriculture","award":["TKII-AMVL001"],"award-info":[{"award-number":["TKII-AMVL001"]}]},{"name":"USDA National Institute of Food and Agriculture","award":["DGTIC-347"],"award-info":[{"award-number":["DGTIC-347"]}]},{"name":"USDA National Institute of Food and Agriculture","award":["1019794"],"award-info":[{"award-number":["1019794"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chia seed peptides (CSP) can be a source of multifunctional biopeptides to treat non-communicable diseases. However, interactions and binding affinity involved in targeting specific receptors remains unexplored. In this study, molecular simulation techniques were used as virtual screening of CSP to determine drug-like candidates using a multi-target-directed ligand approach. CSP fraction with the best bioactivities in vitro was sequenced. Then, a prediction model was built using physicochemical descriptors (hydrophobicity, hydrophilicity, intestinal stability, antiangiogenic, antihypertensive, and anti-inflammatory) to calculate potential scores and rank possible biopeptides. Furthermore, molecular dynamics simulations (MDS) and ensemble molecular docking analysis were carried out using four human protein targets (ACE, angiotensin converting enzyme; VEGF, vascular endothelial growth factor; GLUC, glucocorticoid and MINC, mineralocorticoid receptors). Five known-sequence peptides (NNVFYPF, FNIVFPG, SRPWPIDY, QLQRWFR, GSRFDWTR) and five de novo peptides (DFKF, DLRF, FKAF, FRSF, QFRF) had the lowest energy score and higher affinity for ACE and VEGF. The therapeutic effects of these selected peptides can be related to the inhibition of the enzymes involved in angiogenesis and hypertension, due to formation of stable complexes with VEGF and ACE binding sites, respectively. The application of MDS is a good resource for identifying bioactive peptides for future experimental validation.<\/jats:p>","DOI":"10.3390\/ijms23137288","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:21:50Z","timestamp":1656634910000},"page":"7288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Multifunctional Analysis of Chia Seed (Salvia hispanica L.) Bioactive Peptides Using Peptidomics and Molecular Dynamics Simulations Approaches"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6823-8785","authenticated-orcid":false,"given":"Jos\u00e9 E.","family":"Aguilar-Toal\u00e1","sequence":"first","affiliation":[{"name":"Departamento de Ciencias de la Alimentaci\u00f3n, Divisi\u00f3n de Ciencias Biol\u00f3gicas y de la Salud, Universidad Aut\u00f3noma Metropolitana, Unidad Lerma. Av. de las Garzas 10. Col. El Pante\u00f3n, Lerma de Villada 52005, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5674-7881","authenticated-orcid":false,"given":"Abraham","family":"Vidal-Limon","sequence":"additional","affiliation":[{"name":"Red de Estudios Moleculares Avanzados, Instituto de Ecolog\u00eda A.C. (INECOL), Carretera Antigua a Coatepec 351, El Haya, Xalapa 91073, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0994-1205","authenticated-orcid":false,"given":"Andrea M.","family":"Liceaga","sequence":"additional","affiliation":[{"name":"Protein Chemistry and Bioactive Peptides Laboratory, Department of Food Science, Purdue University, 745 Agriculture Mall Dr., West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1021\/acs.jafc.1c06110","article-title":"Integration of molecular docking analysis and molecular dynamics simulations for studying food proteins and bioactive peptides","volume":"70","author":"Liceaga","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.trac.2018.04.005","article-title":"Advancement and prospects of bioinformatics analysis for studying bioactive peptides from food-derived protein: Sequence, structure, and functions","volume":"105","author":"Tu","year":"2018","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1007\/s00216-018-0974-1","article-title":"Bioinformatics and peptidomics approaches to the discovery and analysis of food-derived bioactive peptides","volume":"410","author":"Agyei","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.tifs.2018.07.011","article-title":"Applications of chia (Salvia hispanica L.) in food products","volume":"80","author":"Zettel","year":"2018","journal-title":"Trends Food Sci. Technol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kulczy\u0144ski, B., Kobus-Cisowska, J., Taczanowski, M., Kmiecik, D., and Gramza-Micha\u0142owska, A. (2019). The chemical composition and ntritional value of Chia seeds-Current state of knowledge. Nutrients, 11.","DOI":"10.3390\/nu11061242"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1039\/C9FO00239A","article-title":"Chia seeds: An ancient grain trending in modern human diets","volume":"10","author":"Melo","year":"2019","journal-title":"Food Funct."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105187","DOI":"10.1016\/j.foodhyd.2019.105187","article-title":"Physicochemical characteristics of chia seed (Salvia hispanica) protein hydrolysates produced using ultrasonication followed by microwave-assisted hydrolysis","volume":"97","author":"Liceaga","year":"2019","journal-title":"Food Hydrocoll."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1007\/s12602-020-09653-8","article-title":"New insights into the antimicrobial properties of hydrolysates and peptide fractions derived from Chia seed (Salvia hispanica L.)","volume":"12","author":"Deering","year":"2020","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s00726-020-02879-4","article-title":"Identification of chia seed (Salvia hispanica L.) peptides with enzyme inhibition activity towards skin-aging enzymes","volume":"52","author":"Liceaga","year":"2020","journal-title":"Amino Acids"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.foodchem.2018.09.061","article-title":"Adding value to the chia (Salvia hispanica L.) expeller: Production of bioactive peptides with antioxidant properties by enzymatic hydrolysis with Papain","volume":"274","author":"Cotabarren","year":"2019","journal-title":"Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11130-018-0668-z","article-title":"Peptides from Chia present atibacterial ativity and inhibit colesterol synthesis","volume":"73","author":"Coelho","year":"2018","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.foodchem.2019.03.036","article-title":"Digested total protein and protein fractions from chia seed (Salvia hispanica L.) had high scavenging capacity and inhibited 5-LOX, COX-1-2, and iNOS enzymes","volume":"289","author":"Grancieri","year":"2019","journal-title":"Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1021\/acs.jcim.2c00089","article-title":"GM-Pep: A high efficiency strategy to de novo design functional peptide sequences","volume":"62","author":"Chen","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e02076","DOI":"10.1016\/j.heliyon.2019.e02076","article-title":"FeptideDB: A web application for new bioactive peptides from food protein","volume":"5","author":"Panyayai","year":"2019","journal-title":"Heliyon"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s11694-020-00434-z","article-title":"Prediction, identification and evaluation of bioactive peptides from tomato seed proteins using in silico approach","volume":"14","author":"Kartal","year":"2020","journal-title":"J. Food Meas. Charact."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Coscueta, E.R., Batista, P., Gomes, J.E., da Silva, R., and Pintado, M.M. (2022). Screening of novel bioactive peptides from goat casein: In silico to in vitro validation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052439"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105163","DOI":"10.1016\/j.dib.2020.105163","article-title":"Data on bioactive peptides derived from chicken hydrolysate with potential alcohol dehydrogenase stabilizing activity and in silico analysis of their potential activity and applicability","volume":"29","author":"Xiao","year":"2020","journal-title":"Data Brief"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.2174\/1381612033454883","article-title":"Bioactive proteins and peptides from food sources. Applications of bioprocesses used in isolation and recovery","volume":"9","author":"Kitts","year":"2003","journal-title":"Curr. Pharm. Des."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R11","DOI":"10.1111\/j.1750-3841.2011.02455.x","article-title":"Food protein-derived bioactive peptides: Production, processing, and potential health benefits","volume":"77","author":"Udenigwe","year":"2012","journal-title":"J. Food Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.tifs.2005.07.003","article-title":"Quantitative structure activity relationship modelling of peptides and proteins as a tool in food science","volume":"16","author":"Pripp","year":"2005","journal-title":"Trends Food Sci. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0022-2836(03)00316-4","article-title":"Molecular dynamics studies of a molecular switch in the glucocorticoid receptor","volume":"328","author":"Stockner","year":"2003","journal-title":"J. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.31557\/APJCP.2019.20.9.2681","article-title":"Identification of potent VEGF inhibitors for the clinical treatment of glioblastoma, a virtual screening approach","volume":"20","author":"Yadav","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103308","DOI":"10.1016\/j.jcs.2021.103308","article-title":"Amaranth proteins as potential source of bioactive peptides with enhanced inhibition of enzymatic markers linked with hypertension and diabetes","volume":"101","author":"Kamal","year":"2021","journal-title":"J. Cereal Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108193","DOI":"10.1016\/j.lwt.2019.05.091","article-title":"Molecular binding mechanism and identification of novel anti-hypertensive and anti-inflammatory bioactive peptides from camel milk protein hydrolysates","volume":"112","author":"Mudgil","year":"2019","journal-title":"LWT Food Sci. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.foodchem.2019.01.010","article-title":"Identification of new bioactive peptides from Kefir milk through proteopeptidomics: Bioprospection of antihypertensive molecules","volume":"282","author":"Amorim","year":"2019","journal-title":"Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Medina-Franco, J.L., and Sald\u00edvar-Gonz\u00e1lez, F.I. (2020). Cheminformatics to characterize pharmacologically active natural products. Biomolecules, 10.","DOI":"10.3390\/biom10111566"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/bs.arcc.2017.06.005","article-title":"Chapter Six\u2014Gaussian Accelerated Molecular Dynamics: Theory, Implementation, and Applications","volume":"Volume 13","author":"Dixon","year":"2017","journal-title":"Annual Reports in Computational Chemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5526","DOI":"10.1021\/acs.jctc.0c00395","article-title":"Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics","volume":"16","author":"Miao","year":"2020","journal-title":"J. Chem. Theory Comput."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1016\/j.str.2015.09.012","article-title":"Ligand binding mechanism in steroid receptors: From conserved plasticity to differential evolutionary constraints","volume":"23","author":"Edman","year":"2015","journal-title":"Structure"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_31","unstructured":"Schr\u00f6dinger (2021). QikProp v 2022-2, LLC."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.proeng.2012.08.252","article-title":"Predicting skin permeability of chemical substances using a quantitative structure-activity relationship","volume":"45","author":"Chang","year":"2012","journal-title":"Procedia Eng."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10076","DOI":"10.1038\/s41598-021-89587-5","article-title":"Correlation between the structure and skin permeability of compounds","volume":"11","author":"Zeng","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"129374","DOI":"10.1016\/j.foodchem.2021.129374","article-title":"Simulated gastrointestinal digestion of camel and bovine casein hydrolysates: Identification and characterization of novel anti-diabetic bioactive peptides","volume":"353","author":"Mudgil","year":"2021","journal-title":"Food Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:41:06Z","timestamp":1760139666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":34,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137288"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137288","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]}}}