{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:02:58Z","timestamp":1793646178951,"version":"4.5.1"},"reference-count":62,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T00:00:00Z","timestamp":1580256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several milk\/whey derived peptides possess high in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. However, in some cases, poor correlation between the in vitro ACE inhibitory activity and the in vivo antihypertensive activity has been observed. The aim of this study is to gain insight into the structure-activity relationship of peptide sequences present in whey\/milk protein hydrolysates with high ACE inhibitory activity, which could lead to a better understanding and prediction of their in vivo antihypertensive activity. The potential interactions between peptides produced from whey proteins, previously reported as high ACE inhibitors such as IPP, LIVTQ, IIAE, LVYPFP, and human ACE were assessed using a molecular docking approach. The results show that peptides IIAE, LIVTQ, and LVYPFP formed strong H bonds with the amino acids Gln 259, His 331, and Thr 358 in the active site of the human ACE. Interestingly, the same residues were found to form strong hydrogen bonds with the ACE inhibitory drug Sampatrilat. Furthermore, peptides IIAE and LVYPFP interacted with the amino acid residues Gln 259 and His 331, respectively, also in common with other ACE-inhibitory drugs such as Captopril, Lisinopril and Elanapril. Additionally, IIAE interacted with the amino acid residue Asp 140 in common with Lisinopril, and LIVTQ interacted with Ala 332 in common with both Lisinopril and Elanapril. The peptides produced naturally from whey by enzymatic hydrolysis interacted with residues of the human ACE in common with potent ACE-inhibitory drugs which suggests that these natural peptides may be potent ACE inhibitors.<\/jats:p>","DOI":"10.3390\/ijms21030864","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T10:51:07Z","timestamp":1580295067000},"page":"864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Whey-Derived Peptides Interactions with ACE by Molecular Docking as a Potential Predictive Tool of Natural ACE Inhibitors"],"prefix":"10.3390","volume":"21","author":[{"given":"Yara","family":"Chamata","sequence":"first","affiliation":[{"name":"Harry Nursten Building, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-8539","authenticated-orcid":false,"given":"Kimberly A.","family":"Watson","sequence":"additional","affiliation":[{"name":"Harborne Building, School of Biological Sciences, University of Reading, Reading RG6 6AP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4438-191X","authenticated-orcid":false,"given":"Paula","family":"Jauregi","sequence":"additional","affiliation":[{"name":"Harry Nursten Building, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,29]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2016, October 20). Cardiovascular Diseases (CVDs): Fact Sheet No.317. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs317\/en\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.jacc.2012.03.074","article-title":"Cardiovascular disease in the developing world","volume":"60","author":"Celermajer","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S1098-3597(09)62037-8","article-title":"Cardiovascular disease and modifiable cardiometabolic risk factors","volume":"9","author":"Cannon","year":"2008","journal-title":"Clin. Cornerstone"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev-food-022814-015520","article-title":"Antihypertensive Peptides from Food Proteins","volume":"6","author":"Aluko","year":"2015","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.1021\/jf900803r","article-title":"Anti-hypertensive Nutraceuticals and Functional Foods","volume":"57","author":"Chen","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/j.idairyj.2007.02.009","article-title":"ACE-inhibitory Activity of Probiotic Yoghurt","volume":"17","author":"Donkor","year":"2007","journal-title":"Int. Dairy J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrd1227","article-title":"Ace revisited: A new target for structure-based drug design","volume":"2","author":"Acharya","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0271-5317(04)00058-2","article-title":"Angiotensin I\u2013converting enzyme inhibitory peptides derived from food proteins and their physiological and pharmacological effects","volume":"24","author":"Li","year":"2004","journal-title":"Nutr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9002","DOI":"10.1016\/S0021-9258(18)31543-6","article-title":"The two homologous domains of human angiotensin I-converting enzyme are both catalytically active","volume":"266","author":"Wei","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1007\/s00018-004-4239-0","article-title":"Structure of angiotensin I-converting enzyme","volume":"61","author":"Sturrock","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nature01370","article-title":"Crystal structure of the human angiotensin-converting enzyme\u2013lisinopril complex","volume":"421","author":"Natesh","year":"2003","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1093\/protein\/gzg122","article-title":"Structure\u2013function discrimination of the N-and C-catalytic domains of human angiotensin-converting enzyme: Implications for Cl\u2013activation and peptide hydrolysis mechanisms","volume":"16","author":"Tzakos","year":"2003","journal-title":"Protein Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"829","DOI":"10.2174\/138161207780363112","article-title":"Technological options for the production of health-promoting proteins and peptides derived from milk and colostrum","volume":"13","author":"Korhonen","year":"2007","journal-title":"Curr. Pharm. Des."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"980S","DOI":"10.1093\/jn\/134.4.980S","article-title":"Hypotensive peptides from milk proteins","volume":"134","author":"FitzGerald","year":"2004","journal-title":"J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1079\/BJN20051570","article-title":"Short-term effect of egg-white hydrolysate products on the arterial blood pressure of hypertensive rats","volume":"94","author":"Miguel","year":"2005","journal-title":"Br. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1517\/14740338.5.5.643","article-title":"Angiotensin-converting enzyme inhibitor-related angioedema: How to deal with it","volume":"5","author":"Beltrami","year":"2006","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/jhh.2010.85","article-title":"Blood pressure lowering effect of lactotripeptides assumed as functional foods: A meta-analysis of current available clinical trials","volume":"25","author":"Cicero","year":"2011","journal-title":"J. Hum. Hypertens."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1017\/S0954422413000139","article-title":"The impact of milk proteins and peptides on blood pressure and vascular function: A review of evidence from human intervention studies","volume":"26","author":"Fekete","year":"2013","journal-title":"Nutr. Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1097\/MOL.0b013e3283333813","article-title":"Lactopeptides and human blood pressure","volume":"21","author":"Geleijnse","year":"2010","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1039\/c2fo10192k","article-title":"Antihypertensive peptides from food proteins: A review","volume":"3","author":"Miralles","year":"2012","journal-title":"Food Funct."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0958-6946(98)00059-4","article-title":"Overview on milk protein-derived peptides","volume":"8","author":"Meisel","year":"1998","journal-title":"Int. Dairy J."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3168\/jds.S0022-0302(95)76689-9","article-title":"Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk","volume":"78","author":"Nakamura","year":"1995","journal-title":"J. Dairy Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.lfs.2010.11.001","article-title":"Casein-derived tripeptide Ile\u2013Pro\u2013Pro improves angiotensin-(1\u20137)-and bradykinin-induced rat mesenteric artery relaxation","volume":"88","author":"Ehlers","year":"2011","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.foodres.2014.01.069","article-title":"Peptidomics for discovery, bioavailability and monitoring of dairy bioactive peptides","volume":"63","author":"Miralles","year":"2014","journal-title":"Food Res. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3390\/ijms16010256","article-title":"Molecular targets of antihypertensive peptides: Understanding the mechanisms of action based on the pathophysiology of hypertension","volume":"16","author":"Majumder","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jff.2014.03.002","article-title":"Mechanisms of food protein-derived antihypertensive peptides other than ACE inhibition","volume":"8","author":"Udenigwe","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/ajg.2015.119","article-title":"Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs","volume":"110","author":"Masclee","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10911-015-9334-3","article-title":"Proteolytic systems in milk: Perspectives on the evolutionary function within the mammary gland and the infant","volume":"20","author":"Dallas","year":"2015","journal-title":"J. Mammary Gland Biol. Neoplasia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.2174\/1381612033454847","article-title":"Biofunctional peptides from milk proteins: Mineral binding and cytomodulatory effects","volume":"9","author":"Meisel","year":"2003","journal-title":"Curr. Pharm. Des."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1016\/j.foodchem.2012.03.113","article-title":"Chemical characterisation and determination of sensory attributes of hydrolysates produced by enzymatic hydrolysis of whey proteins following a novel integrative process","volume":"134","author":"Welderufael","year":"2012","journal-title":"Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1263\/jbb.106.310","article-title":"Angiotensin-I converting enzyme (ACE) inhibitory mechanism of tripeptides containing aromatic residues","volume":"106","author":"Kobayashi","year":"2008","journal-title":"J. Biosci. Bioeng."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3898","DOI":"10.1016\/j.bmcl.2011.05.033","article-title":"The molecular mechanisms of interactions between bioactive peptides and angiotensin-converting enzyme","volume":"21","author":"Pan","year":"2011","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tifs.2014.02.004","article-title":"Bioinformatics approaches, prospects and challenges of food bioactive peptide research","volume":"36","author":"Udenigwe","year":"2014","journal-title":"Trends Food Sci. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jff.2017.03.015","article-title":"Sequence analysis and molecular docking of antithrombotic peptides from casein hydrolysate by trypsin digestion","volume":"32","author":"Tu","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.foodchem.2016.10.087","article-title":"Identification, functional gastrointestinal stability and molecular docking studies of lentil peptides with dual antioxidant and angiotensin I converting enzyme inhibitory activities","volume":"221","author":"Bonache","year":"2017","journal-title":"Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.procbio.2017.08.009","article-title":"Angiotensin I-converting enzyme inhibitory peptides from Sipuncula (Phascolosoma esculenta): Purification, identification, molecular docking and antihypertensive effects on spontaneously hypertensive rats","volume":"63","author":"Guo","year":"2017","journal-title":"Process Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.jff.2018.04.020","article-title":"Transepithelial transport and structural changes of chicken angiotensin I-converting enzyme (ACE) inhibitory peptides through Caco-2 cell monolayers","volume":"45","author":"Sangsawad","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s11802-017-3201-3","article-title":"Characterization of angiotensin-I converting enzyme inhibiting peptide from Venerupis philippinarum with nano-liquid chromatography in combination with orbitrap mass spectrum detection and molecular docking","volume":"16","author":"Shi","year":"2017","journal-title":"J. Ocean Univ. China"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.lwt.2016.08.047","article-title":"A novel antioxidant and ACE inhibitory peptide from rice bran protein: Biochemical characterization and molecular docking study","volume":"75","author":"Wang","year":"2017","journal-title":"Lwt-Food Sci. Technol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.foodchem.2015.12.012","article-title":"Production of ACE inhibitory peptides from sweet sorghum grain protein using alcalase: Hydrolysis kinetic, purification and molecular docking study","volume":"199","author":"Wu","year":"2016","journal-title":"Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yu, Z., Chen, Y., Zhao, W., Li, J., Liu, J., and Chen, F. (2018). Identification and molecular docking study of novel angiotensin-converting enzyme inhibitory peptides from Salmo salar using in silico methods. J. Sci. Food Agric.","DOI":"10.1002\/jsfa.8908"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.foodchem.2017.02.032","article-title":"Empirical and bioinformatic characterization of buffalo (Bubalus bubalis) colostrum whey peptides & their angiotensin I-converting enzyme inhibition","volume":"228","author":"Ashok","year":"2017","journal-title":"Food Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jff.2017.03.008","article-title":"Novel angiotensin I-converting enzyme inhibitory peptides from protease hydrolysates of Qula casein: Quantitative structure-activity relationship modeling and molecular docking study","volume":"32","author":"Lin","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Nongonierma, A.B., and FitzGerald, R.J. (2017). Strategies for the discovery and identification of food protein-derived biologically active peptides. Trends Food Sci. Technol.","DOI":"10.1016\/j.tifs.2017.03.003"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9386","DOI":"10.1073\/pnas.85.24.9386","article-title":"Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning","volume":"85","author":"Soubrier","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1111\/febs.14421","article-title":"Crystal structures of sampatrilat and sampatrilat-Asp in complex with human ACE\u2013a molecular basis for domain selectivity","volume":"285","author":"Cozier","year":"2018","journal-title":"Febs J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.foodchem.2018.02.107","article-title":"Identification of a novel ACE-inhibitory peptide from casein and evaluation of the inhibitory mechanisms","volume":"256","author":"Tu","year":"2018","journal-title":"Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5251","DOI":"10.1039\/C8FO00569A","article-title":"Preparation and identification of novel inhibitory Angiotensin-I-converting enzyme peptides from tilapia skin gelatin hydrolysates: Inhibition kinetics and molecular docking","volume":"9","author":"Ling","year":"2018","journal-title":"Food Funct."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0731-7085(97)00127-1","article-title":"Clinical analysis of sampatrilat, a combined renal endopeptidase and angiotensin-converting enzyme inhibitor: II: Assay in the plasma and urine of human volunteers by dissociation enhanced lanthanide fluorescence immunoassay (DELFIA)","volume":"16","author":"Venn","year":"1998","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0009-9236(98)90075-3","article-title":"Combined inhibition of neutral endopeptidase and angiotensin-converting enzyme by sampatrilat in essential hypertension","volume":"64","author":"Wallis","year":"1998","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8718","DOI":"10.1021\/bi049480n","article-title":"Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme","volume":"43","author":"Natesh","year":"2004","journal-title":"Biochemistry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.peptides.2009.05.029","article-title":"Ala-Val-Phe and Val-Phe: ACE inhibitory peptides derived from insect protein with antihypertensive activity in spontaneously hypertensive rats","volume":"31","author":"Vercruysse","year":"2010","journal-title":"Peptides"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1671-2927(11)60026-6","article-title":"A novel angiotensin I converting enzyme inhibitory peptide from the milk casein: Virtual screening and docking studies","volume":"10","author":"Wang","year":"2011","journal-title":"Agric. Sci. China"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ijfoodmicro.2013.09.002","article-title":"Novel probiotic-fermented milk with angiotensin I-converting enzyme inhibitory peptides produced by Bifidobacterium bifidum MF 20\/5","volume":"167","author":"Gibson","year":"2013","journal-title":"Int. J. Food Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nm0603-685","article-title":"Molecular regulation of vessel maturation","volume":"9","author":"Jain","year":"2003","journal-title":"Nat. Med."},{"key":"ref_57","unstructured":"Schrodinger LLC (2015). Version 1.8, The PyMOL Molecular Graphics System, Schr\u00f6dinger LLC. Technical Report."},{"key":"ref_58","unstructured":"(2019, December 02). PDBeFold - Structure Similarity, Embl-Ebi. Available online: http:\/\/www.ebi.ac.uk\/msd-srv\/ssm\/cgi-bin\/ssmserver."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1021\/jm0203783","article-title":"Comparative evaluation of 11 scoring functions for molecular docking","volume":"46","author":"Wang","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"54","DOI":"10.4103\/0250-474X.180251","article-title":"CoMFA, CoMSIA, HQSAR and molecular docking analysis of ionone-based chalcone derivatives as antiprostate cancer activity","volume":"78","author":"Sharma","year":"2016","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.3390\/ijms12031605","article-title":"Combined 3D-QSAR modeling and molecular docking studies on Pyrrole-Indolin-2-ones as Aurora A Kinase inhibitors","volume":"12","author":"Ai","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ejmech.2010.10.017","article-title":"Molecular modeling studies on imidazo [4, 5-b] pyridine derivatives as Aurora A kinase inhibitors using 3D-QSAR and docking approaches","volume":"46","author":"Lan","year":"2011","journal-title":"Eur. J. Med. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/864\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:02Z","timestamp":1760172782000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,29]]},"references-count":62,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ijms21030864"],"URL":"https:\/\/doi.org\/10.3390\/ijms21030864","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,29]]}}}