{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:31:11Z","timestamp":1788269471663,"version":"build-2803163510"},"reference-count":101,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,11]],"date-time":"2020-01-11T00:00:00Z","timestamp":1578700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1170718"],"award-info":[{"award-number":["1170718"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The angiotensin-converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase, which has a direct involvement in the control of blood pressure by performing the hydrolysis of angiotensin I to produce angiotensin II. At the same time, ACE hydrolyzes other substrates such as the vasodilator peptide bradykinin and the anti-inflammatory peptide N-acetyl-SDKP. In this sense, ACE inhibitors are bioactive substances with potential use as medicinal products for treatment or prevention of hypertension, heart failures, myocardial infarction, and other important diseases. This review examined the most recent literature reporting ACE inhibitors with the help of molecular modeling. The examples exposed here demonstrate that molecular modeling methods, including docking, molecular dynamics (MD) simulations, quantitative structure-activity relationship (QSAR), etc, are essential for a complete structural picture of the mode of action of ACE inhibitors, where molecular docking has a key role. Examples show that too many works identified ACE inhibitory activities of natural peptides and peptides obtained from hydrolysates. In addition, other works report non-peptide compounds extracted from natural sources and synthetic compounds. In all these cases, molecular docking was used to provide explanation of the chemical interactions between inhibitors and the ACE binding sites. For docking applications, most of the examples exposed here do not consider that: (i) ACE has two domains (nACE and cACE) with available X-ray structures, which are relevant for the design of selective inhibitors, and (ii) nACE and cACE binding sites have large dimensions, which leads to non-reliable solutions during docking calculations. In support of the solution of these problems, the structural information found in Protein Data Bank (PDB) was used to perform an interaction fingerprints (IFPs) analysis applied on both nACE and cACE domains. This analysis provides plots that identify the chemical interactions between ligands and both ACE binding sites, which can be used to guide docking experiments in the search of selective natural components or novel drugs. In addition, the use of hydrogen bond constraints in the S2 and S2\u2032 subsites of nACE and cACE are suggested to guarantee that docking solutions are reliable.<\/jats:p>","DOI":"10.3390\/molecules25020295","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T04:05:51Z","timestamp":1578888351000},"page":"295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-1444","authenticated-orcid":false,"given":"Julio","family":"Caballero","sequence":"first","affiliation":[{"name":"Centro de Bioinform\u00e1tica y Simulaci\u00f3n Molecular (CBSM), Universidad de Talca, 1 Poniente No. 1141, Casilla 721, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev.bi.45.070176.000445","article-title":"Angiotensin-converting enzyme and the regulation of vasoactive peptides","volume":"45","author":"Soffer","year":"1976","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1126\/science.191908","article-title":"Design of specific inhibitors of angiotensin-converting enzyme: New class of orally active antihypertensive agents","volume":"196","author":"Ondetti","year":"1977","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5484","DOI":"10.1021\/bi00644a014","article-title":"Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids","volume":"16","author":"Cushman","year":"1977","journal-title":"Biochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0008-6363(95)00006-2","article-title":"The discovery of captopril: From large animals to small molecules","volume":"30","author":"Opie","year":"1995","journal-title":"Cardiovasc. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1021\/bi00815a005","article-title":"Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom","volume":"9","author":"Ferreira","year":"1970","journal-title":"Biochemistry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1007\/BF01930447","article-title":"Inhibition of angiotensin-coverting enzyme by analogs of peptides from Bothrops jararaca venom","volume":"29","author":"Cushman","year":"1973","journal-title":"Experientia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1365-2125.1982.tb01991.x","article-title":"Enalapril maleate and a lysine analogue (MK-521): Disposition in man","volume":"14","author":"Ulm","year":"1982","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2165\/00003088-200241030-00005","article-title":"Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: An update","volume":"41","author":"Song","year":"2002","journal-title":"Clin Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1592\/phco.22.1.27.33502","article-title":"A review of vasopeptidase inhibitors: A new modality in the treatment of hypertension and chronic heart failure","volume":"22","author":"Nathisuwan","year":"2002","journal-title":"Pharmacotherapy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/S0140-6736(97)09137-X","article-title":"Plasma bradykinin in angio-oedema","volume":"351","author":"Nussberger","year":"1998","journal-title":"The Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.coph.2010.11.001","article-title":"Different in vivo functions of the two catalytic domains of angiotensin-converting enzyme (ACE)","volume":"11","author":"Bernstein","year":"2011","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1161\/HYPERTENSIONAHA.107.097865","article-title":"Angiotensin-converting enzyme C-terminal catalytic domain is the main site of angiotensin I cleavage in vivo","volume":"51","author":"Fuchs","year":"2008","journal-title":"Hypertension"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.phrs.2018.07.006","article-title":"The anti-inflammatory peptide Ac-SDKP: Synthesis, role in ACE inhibition, and its therapeutic potential in hypertension and cardiovascular diseases","volume":"134","author":"Kumar","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/S0140-6736(00)02596-4","article-title":"Vasopeptidase inhibition and angio-oedema","volume":"356","author":"Messerli","year":"2000","journal-title":"The Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6065","DOI":"10.1021\/bi012121x","article-title":"Selective inhibition of the C-domain of angiotensin I converting enzyme by bradykinin potentiating peptides","volume":"41","author":"Cotton","year":"2002","journal-title":"Biochemistry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"H1226","DOI":"10.1152\/ajpheart.00305.2007","article-title":"Novel anti-inflammatory mechanisms of N-Acetyl-Ser-Asp-Lys-Pro in hypertension-induced target organ damage","volume":"294","author":"Sharma","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1073\/pnas.96.8.4330","article-title":"RXP 407, a phosphinic peptide, is a potent inhibitor of angiotensin I converting enzyme able to differentiate between its two active sites","volume":"96","author":"Dive","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8048","DOI":"10.1021\/bi049504q","article-title":"Structural determinants of RXPA380, a potent and highly selective inhibitor of the angiotensin-converting enzyme C-domain","volume":"43","author":"Georgiadis","year":"2004","journal-title":"Biochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35685","DOI":"10.1074\/jbc.M110.167866","article-title":"The N domain of human angiotensin-I-converting enzyme: The role of N-glycosylation and the crystal structure in complex with an N domain-specific phosphinic inhibitor, RXP407","volume":"285","author":"Anthony","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ejmech.2019.07.009","article-title":"Discovery, synthesis, and in vitro evaluation of a novel bioactive peptide for ACE and DPP-IV inhibitory activity","volume":"180","author":"Ashok","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1007\/s10989-018-09802-2","article-title":"Camel and horse milk casein hydrolysates exhibit angiotensin converting enzyme inhibitory and antioxidative effects in vitro and in silico","volume":"25","author":"Ugwu","year":"2019","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1021\/acs.jafc.7b04294","article-title":"Antihypertensive effects, molecular docking study, and isothermal titration calorimetry assay of angiotensin I-converting enzyme inhibitory peptides from chlorella vulgaris","volume":"66","author":"Xie","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11202","DOI":"10.1021\/acs.jafc.7b04442","article-title":"Ultrafast Screening of a Novel, Moderately Hydrophilic Angiotensin-Converting-Enzyme-Inhibitory Peptide, RYL, from Silkworm Pupa Using an Fe-Doped-Silkworm-Excrement-Derived Biocarbon: Waste Conversion by Waste","volume":"65","author":"Liu","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.jprot.2015.08.018","article-title":"Screening, discovery, and characterization of angiotensin-I converting enzyme inhibitory peptides derived from proteolytic hydrolysate of bitter melon seed proteins","volume":"128","author":"Priyanto","year":"2015","journal-title":"J. Proteom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-50619-w","article-title":"Molecular insights into the interaction of hemorphin and its targets","volume":"9","author":"Ali","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8149","DOI":"10.1021\/acs.jafc.9b02276","article-title":"Isolation and Characterization of Three Antihypertension Peptides from the Mycelia of Ganoderma Lucidum (Agaricomycetes)","volume":"67","author":"Wu","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gao, X., Li, X., Yan, P., Sun, R., Kan, G., and Zhou, Y. (2018). Identification and Functional Mechanism of Novel Angiotensin I Converting Enzyme Inhibitory Dipeptides from Xerocomus badius Cultured in Shrimp Processing Waste Medium. Biomed Res. Int., 2018.","DOI":"10.1155\/2018\/5089270"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8737","DOI":"10.1021\/acs.jafc.8b03648","article-title":"Characterization of Angiotensin-Converting Enzyme Inhibitory Activity of X-Hyp-Gly-Type Tripeptides: Importance of Collagen-Specific Prolyl Hydroxylation","volume":"66","author":"Taga","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1111\/1750-3841.14299","article-title":"Novel Angiotensin-Converting Enzyme Inhibitory Peptides Derived from Oncorhynchus mykiss Nebulin: Virtual Screening and In Silico Molecular Docking Study","volume":"83","author":"Yu","year":"2018","journal-title":"J. Food Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yu, D., Wang, C., Song, Y., Zhu, J., and Zhang, X. (2019). Discovery of Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Todarodes pacificus and Their Inhibitory Mechanism: In Silico and In Vitro Studies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174159"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1021\/acs.jafc.8b00313","article-title":"Quantitative Structure-Activity Relationship Modeling Coupled with Molecular Docking Analysis in Screening of Angiotensin I-Converting Enzyme Inhibitory Peptides from Qula Casein Hydrolysates Obtained by Two-Enzyme Combination Hydrolysis","volume":"66","author":"Lin","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Li, J., Liu, Z., Zhao, Y., Zhu, X., Yu, R., Dong, S., and Wu, H. (2018). Novel Natural Angiotensin Converting Enzyme (ACE)-Inhibitory Peptides Derived from Sea Cucumber-Modified Hydrolysates by Adding Exogenous Proline and a Study of Their Structure\u2013Activity Relationship. Mar. Drugs, 16.","DOI":"10.3390\/md16080271"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.lwt.2019.04.053","article-title":"Novel angiotensin-converting enzyme inhibitory peptides derived from Trichiurus lepturus myosin: Molecular docking and surface plasmon resonance study","volume":"110","author":"Fu","year":"2019","journal-title":"LWT"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.foodchem.2017.06.112","article-title":"In silico analysis and molecular docking study of angiotensin I-converting enzyme inhibitory peptides from smooth-hound viscera protein hydrolysates fractionated by ultrafiltration","volume":"239","author":"Abdelhedi","year":"2018","journal-title":"Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.jfda.2017.07.008","article-title":"Production of antioxidant and ACE-inhibitory peptides from Kluyveromyces marxianus protein hydrolysates: Purification and molecular docking","volume":"26","author":"Mirzaei","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"ref_37","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_38","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_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phymed.2017.09.013","article-title":"Identification and in silico characterization of a novel peptide inhibitor of angiotensin converting enzyme from pigeon pea (Cajanus cajan)","volume":"36","author":"Nawaz","year":"2017","journal-title":"Phytomedicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1021\/acs.jafc.8b00732","article-title":"Analysis and Evaluation of the Inhibitory Mechanism of a Novel Angiotensin-I-Converting Enzyme Inhibitory Peptide Derived from Casein Hydrolysate","volume":"66","author":"Tu","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3648","DOI":"10.1080\/07391102.2016.1264892","article-title":"Multi-spectroscopic and molecular modeling studies of interaction between two different angiotensin I converting enzyme inhibitory peptides from gluten hydrolysate and human serum albumin","volume":"35","author":"Shareghi","year":"2017","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zarei, M., Abidin, N.B.Z., Auwal, S.M., Chay, S.Y., Haiyee, Z.A., Sikin, A.M., and Saari, N. (2019). 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. Biomolecules, 9.","DOI":"10.3390\/biom9100569"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1039\/C7FO01388D","article-title":"Production, optimisation and characterisation of angiotensin converting enzyme inhibitory peptides from sea cucumber (Stichopus japonicus) gonad","volume":"9","author":"Zhong","year":"2018","journal-title":"Food Funct."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, C., Tu, M., Wu, D., Chen, H., Chen, C., Wang, Z., and Jiang, L. (2018). Identification of an ACE-Inhibitory Peptide from Walnut Protein and Its Evaluation of the Inhibitory Mechanism. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041156"},{"key":"ref_45","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_46","doi-asserted-by":"crossref","unstructured":"Yu, F., Zhang, Z., Luo, L., Zhu, J., Huang, F., Yang, Z., Tang, Y., and Ding, G. (2018). Identification and Molecular Docking Study of a Novel Angiotensin-I Converting Enzyme Inhibitory Peptide Derived from Enzymatic Hydrolysates of Cyclina sinensis. Mar. Drugs, 16.","DOI":"10.3390\/md16110411"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sun, S., Xu, X., Sun, X., Zhang, X., Chen, X., and Xu, N. (2019). Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis. Mar. Drugs, 17.","DOI":"10.3390\/md17030179"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Joel, C.H., Sutopo, C.C.Y., Prajitno, A., Su, J.-H., and Hsu, J.-L. (2018). Screening of Angiotensin-I Converting Enzyme Inhibitory Peptides Derived from Caulerpa lentillifera. Molecules, 23.","DOI":"10.3390\/molecules23113005"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/jb\/mvz029","article-title":"A novel angiotensin-I converting enzyme inhibitory peptide derived from the glutelin of vinegar soaked black soybean and its antihypertensive effect in spontaneously hypertensive rats","volume":"166","author":"Zhang","year":"2019","journal-title":"J. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Marseglia, A., Dellafiora, L., Prandi, B., Lolli, V., Sforza, S., Cozzini, P., Tedeschi, T., Galaverna, G., and Caligiani, A. (2019). Simulated Gastrointestinal Digestion of Cocoa: Detection of Resistant Peptides and In Silico\/In Vitro Prediction of Their Ace Inhibitory Activity. Nutrients, 11.","DOI":"10.3390\/nu11050985"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s11130-019-00754-6","article-title":"Broken Rice as a Potential Functional Ingredient with Inhibitory Activity of Renin and Angiotensin-Converting Enzyme (ACE)","volume":"74","author":"Pinciroli","year":"2019","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.bioorg.2017.09.006","article-title":"The inhibitory activity of HL-7 and HL-10 peptide from scorpion venom (Hemiscorpius lepturus) on angiotensin converting enzyme: Kinetic and docking study","volume":"75","author":"Asoodeh","year":"2017","journal-title":"Bioorg. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.bioorg.2019.04.003","article-title":"Antioxidant and angiotensin-converting enzyme (ACE) inhibitory activity of thymosin alpha-1 (Th\u03b11) peptide","volume":"87","author":"Asoodeh","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.peptides.2018.11.002","article-title":"Active-site directed peptide l-Phe-d-His-l-Leu inhibits angiotensin converting enzyme activity and dexamethasone-induced hypertension in rats","volume":"112","author":"Savitha","year":"2019","journal-title":"Peptides"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.foodchem.2017.10.095","article-title":"Exploration of the molecular interactions between angiotensin-I-converting enzyme (ACE) and the inhibitory peptides derived from hazelnut (Corylus heterophylla Fisch.)","volume":"245","author":"Liu","year":"2018","journal-title":"Food Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13414","DOI":"10.1021\/acs.jafc.8b04303","article-title":"Studies on the Interaction between Angiotensin-Converting Enzyme (ACE) and ACE Inhibitory Peptide from Saurida elongata","volume":"66","author":"Lan","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1080\/08927022.2018.1557327","article-title":"Insight into the binding of ACE-inhibitory peptides to angiotensin-converting enzyme: A molecular simulation","volume":"45","author":"Jiang","year":"2019","journal-title":"Mol. Simul."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1600157","DOI":"10.1002\/minf.201600157","article-title":"Studies on the Bioactivities of ACE-inhibitory Peptides with Phenylalanine C-terminus Using 3D-QSAR, Molecular Docking and in vitro Evaluation","volume":"36","author":"Qi","year":"2017","journal-title":"Mol. Inform."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.molliq.2017.11.033","article-title":"Molecular mechanism of interactions between inhibitory tripeptide GEF and angiotensin-converting enzyme in aqueous solutions by molecular dynamic simulations","volume":"249","author":"Qi","year":"2018","journal-title":"J. Mol. Liq."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Fang, L., Geng, M., Liu, C., Wang, J., Min, W., and Liu, J. (2019). Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215609"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1501023","DOI":"10.1002\/minf.201501023","article-title":"A New Descriptor of Amino Acids-SVGER and its Applications in Peptide QSAR","volume":"36","author":"Tong","year":"2017","journal-title":"Mol. Inform."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9774","DOI":"10.1021\/acs.jafc.7b03367","article-title":"New Quantitative Structure-Activity Relationship Model for Angiotensin-Converting Enzyme Inhibitory Dipeptides Based on Integrated Descriptors","volume":"65","author":"Deng","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5375","DOI":"10.1021\/acs.jafc.6b01631","article-title":"Spermidine Derivatives in Lulo (Solanum quitoense Lam.) Fruit: Sensory (Taste) versus Biofunctional (ACE-Inhibition) Properties","volume":"64","author":"Forero","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.enzmictec.2018.10.010","article-title":"Evaluation of angiotensin converting enzyme inhibitors by SPR biosensor and theoretical studies","volume":"120","author":"Salehabadi","year":"2019","journal-title":"Enzym. Microb. Technol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.foodres.2018.07.035","article-title":"Previously undescribed antioxidative O-heterocyclic angiotensin converting enzyme inhibitors from the intertidal seaweed Sargassum wightii as potential antihypertensives","volume":"113","author":"Maneesh","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.phytol.2015.04.021","article-title":"Structure\u2013activity relationship and inhibition pattern of reishi-derived (Ganoderma lingzhi) triterpenoids against angiotensin-converting enzyme","volume":"12","author":"Shimizu","year":"2015","journal-title":"Phytochem. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ali, M.Y., Seong, S.H., Jung, H.A., and Choi, J.S. (2019). Angiotensin-I-Converting Enzyme Inhibitory Activity of Coumarins from Angelica decursiva. Molecules, 24.","DOI":"10.3390\/molecules24213937"},{"key":"ref_68","first-page":"25","article-title":"Angiotensin-converting enzyme inhibitory activity of polyphenolic compounds from Peperomia pellucida (L) Kunth: An in silico molecular docking study","volume":"9","author":"Ahmad","year":"2019","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1007\/s12539-017-0243-6","article-title":"In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5","volume":"10","author":"Arya","year":"2018","journal-title":"Interdiscip. Sci. Comput. Life Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"19550","DOI":"10.1039\/C4RA00856A","article-title":"Binding mode prediction and identification of new lead compounds from natural products as renin and angiotensin converting enzyme inhibitors","volume":"4","author":"Moorthy","year":"2014","journal-title":"RSC Adv."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"172638","DOI":"10.1016\/j.ejphar.2019.172638","article-title":"Dipeptidyl peptidase-4 inhibitors can inhibit angiotensin converting enzyme","volume":"862","author":"Abouelkheir","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.molstruc.2018.12.008","article-title":"Design, synthesis and biological evaluation of Schiff bases of 4-amino-1,2,4-triazole derivatives as potent angiotensin converting enzyme inhibitors and antioxidant activities","volume":"1180","author":"Saadaoui","year":"2019","journal-title":"J. Mol. Struct."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.bioorg.2017.11.004","article-title":"Design, synthesis of novel Triazolones and bis-Triazolones derivatives under ultrasound irradiation and evaluation as potent angiotensin converting enzyme (ACE) inhibitors","volume":"76","author":"Hamzaoui","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.ejmech.2017.09.076","article-title":"Therapeutic investigations of novel indoxyl-based indolines: A drug target validation and Structure-Activity Relationship of angiotensin-converting enzyme inhibitors with cardiovascular regulation and thrombolytic potential","volume":"141","author":"Manikandan","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1080\/1062936X.2018.1485737","article-title":"Development of non-peptide ACE inhibitors as novel and potent cardiovascular therapeutics: An in silico modelling approach","volume":"29","year":"2018","journal-title":"SAR QSAR Environ. Res."},{"key":"ref_76","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_77","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1021\/acs.jcim.6b00524","article-title":"The Dynamic Nonprime Binding of Sampatrilat to the C-Domain of Angiotensin-Converting Enzyme","volume":"56","author":"Sharma","year":"2016","journal-title":"J. Chem. Inf. Model"},{"key":"ref_78","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\u2014A molecular basis for domain selectivity","volume":"285","author":"Cozier","year":"2018","journal-title":"FEBS J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1021\/jm061259g","article-title":"SHOP: Scaffold HOPping by GRID-based similarity searches","volume":"50","author":"Bergmann","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1021\/ci800391v","article-title":"SHOP: Receptor-based scaffold HOPping by GRID-based similarity searches","volume":"49","author":"Bergmann","year":"2009","journal-title":"J. Chem. Inf. Model"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1042\/CS20130403","article-title":"Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors","volume":"126","author":"Douglas","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1021\/acs.jmedchem.7b01478","article-title":"The Design and Development of a Potent and Selective Novel Diprolyl Derivative That Binds to the N-Domain of Angiotensin-I Converting Enzyme","volume":"61","author":"Fienberg","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_83","unstructured":"(2013, July 22). GOSTAR Drug Database and Clinical Candidate Database; Excelra Knowledge Solutions: Hyderabad, India. Available online: https:\/\/www.gostardb.com\/index.jsp."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Vel\u00e1zquez-Libera, J.L., Navarro-Retamal, C., and Caballero, J. (2018). Insights into the Structural Requirements of 2(S)-Amino-6-Boronohexanoic Acid Derivatives as Arginase I Inhibitors: 3D-QSAR, Docking, and Interaction Fingerprint Studies. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102956"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s10822-018-0173-3","article-title":"Mycobacterium tuberculosis serine\/threonine protein kinases: Structural information for the design of their specific ATP-competitive inhibitors","volume":"32","author":"Caballero","year":"2018","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"496","DOI":"10.3389\/fchem.2019.00496","article-title":"Docking, Interaction Fingerprint, and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) of Sigma1 Receptor Ligands, Analogs of the Neuroprotective Agent RC-33","volume":"7","author":"Rossino","year":"2019","journal-title":"Front Chem."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Vel\u00e1zquez-Libera, J.L., Murillo-L\u00f3pez, J.A., de la Torre, A.F., and Caballero, J. (2019). Structural Requirements of N-alpha-Mercaptoacetyl Dipeptide (NAMdP) Inhibitors of Pseudomonas Aeruginosa Virulence Factor LasB: 3D-QSAR, Molecular Docking, and Interaction Fingerprint Studies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246133"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1021\/jm030331x","article-title":"Structural interaction fingerprint (SIFt): A novel method for analyzing three-dimensional protein-ligand binding interactions","volume":"47","author":"Deng","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1747-0285.2005.00323.x","article-title":"Structural interaction fingerprints: A new approach to organizing, mining, analyzing, and designing protein-small molecule complexes","volume":"67","author":"Singh","year":"2006","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1042\/BJ20100056","article-title":"Characterization of domain-selective inhibitor binding in angiotensin-converting enzyme using a novel derivative of lisinopril","volume":"428","author":"Watermeyer","year":"2010","journal-title":"Biochem. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4616","DOI":"10.1016\/j.bmcl.2006.06.004","article-title":"Synthesis and molecular modeling of a lisinopril-tryptophan analogue inhibitor of angiotensin I-converting enzyme","volume":"16","author":"Nchinda","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_92","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_93","doi-asserted-by":"crossref","first-page":"5942","DOI":"10.1021\/bi8002605","article-title":"Probing the basis of domain-dependent inhibition using novel ketone inhibitors of Angiotensin-converting enzyme","volume":"47","author":"Watermeyer","year":"2008","journal-title":"Biochemistry"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra Precision Glide:\u2009 Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein\u2013Ligand Complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1160\/TH13-05-0386","article-title":"Protective mechanisms of adenosine 5\u2032-monophosphate in platelet activation and thrombus formation","volume":"111","author":"Fuentes","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Fuentes, E., Pereira, J., Mezzano, D., Alarc\u00f3n, M., Caballero, J., and Palomo, I. (2014). Inhibition of platelet activation and thrombus formation by adenosine and inosine: Studies on their relative contribution and molecular modeling. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112741"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Fuentes, E., Caballero, J., Alarc\u00f3n, M., Rojas, A., and Palomo, I. (2014). Chlorogenic Acid Inhibits Human Platelet Activation and Thrombus Formation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090699"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Quesada-Romero, L., Mena-Ulecia, K., Tiznado, W., and Caballero, J. (2014). Insights into the interactions between maleimide derivates and GSK3\u03b2 combining molecular docking and QSAR. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102212"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"64756","DOI":"10.1039\/C6RA12084A","article-title":"Computational study of the binding orientation and affinity of PPAR\u03b3 agonists: Inclusion of ligand-induced fit by cross-docking","volume":"6","author":"Fuentes","year":"2016","journal-title":"RSC Adv."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez, D., and Caballero, J. (2018). Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data?. Molecules, 23.","DOI":"10.3390\/molecules23051038"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/2\/295\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:04:28Z","timestamp":1760364268000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/2\/295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,11]]},"references-count":101,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["molecules25020295"],"URL":"https:\/\/doi.org\/10.3390\/molecules25020295","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,11]]}}}