{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:42:24Z","timestamp":1793644944753,"version":"4.5.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100006013","name":"United Arab Emirates University","doi-asserted-by":"publisher","award":["12R107"],"award-info":[{"award-number":["12R107"]}],"id":[{"id":"10.13039\/501100006013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-78893-3","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T09:08:10Z","timestamp":1732093690000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Molecular insights into the inhibition of angiotensin-converting enzyme 1 by hemopressin peptides"],"prefix":"10.1038","volume":"14","author":[{"given":"Priya","family":"Antony","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bincy","family":"Baby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaesha","family":"Rahma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamaa Abdul","family":"Samad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusra Al","family":"Dhaheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjit","family":"Vijayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"78893_CR1","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1161\/HYPERTENSIONAHA.119.14240","volume":"75","author":"FD Fuchs","year":"2020","unstructured":"Fuchs, F. D. & Whelton, P. K. High blood pressure and cardiovascular disease. Hypertension. 75, 285\u2013292 (2020).","journal-title":"Hypertension"},{"key":"78893_CR2","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1161\/CIRCRESAHA.116.303587","volume":"116","author":"L Te Riet","year":"2015","unstructured":"Te Riet, L., van Esch, J. H. M., Roks, A. J. M., van den Meiracker, A. H. & Danser, A. H. J. Hypertension: renin-angiotensin-aldosterone system alterations. Circ. Res. 116, 960\u2013975 (2015).","journal-title":"Circ. Res."},{"key":"78893_CR3","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.cca.2021.10.029","volume":"524","author":"V Khurana","year":"2022","unstructured":"Khurana, V. & Goswami, B. Angiotensin converting enzyme (ACE). Clin. Chim. Acta. 524, 113\u2013122 (2022).","journal-title":"Clin. Chim. Acta"},{"key":"78893_CR4","doi-asserted-by":"publisher","first-page":"15377","DOI":"10.1016\/S0021-9258(18)98626-6","volume":"266","author":"C Hubert","year":"1991","unstructured":"Hubert, C., Houot, A. M., Corvol, P. & Soubrier, F. Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J. Biol. Chem. 266, 15377\u201315383 (1991).","journal-title":"J. Biol. Chem."},{"key":"78893_CR5","doi-asserted-by":"publisher","unstructured":"Royster, R. L., Groban, L., Locke, A. Q., Morris, B. N. & Slaughter, T. F. Cardiovascular Pharmacology. in Kaplan\u2019s Essentials of Cardiac Anesthesia 132\u2013166, Elsevier (2018). doi:  https:\/\/doi.org\/10.1016\/B978-0-323-49798-5.00008-5","DOI":"10.1016\/B978-0-323-49798-5.00008-5"},{"key":"78893_CR6","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1161\/HYPERTENSIONAHA.107.097865","volume":"51","author":"S Fuchs","year":"2008","unstructured":"Fuchs, S. et al. Angiotensin-converting enzyme C-terminal catalytic domain is the main site of angiotensin I cleavage in vivo. Hypertension. 51, 267\u2013274 (2008).","journal-title":"Hypertension"},{"key":"78893_CR7","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s42485-023-00106-8","volume":"14","author":"OA Olalere","year":"2023","unstructured":"Olalere, O. A., Yap, P. G. & Gan, C. Y. Comprehensive review on some food-derived bioactive peptides with anti-hypertension therapeutic potential for angiotensin-converting enzyme (ACE) inhibition. J. Proteins Proteom. 14, 129\u2013161 (2023).","journal-title":"J. Proteins Proteom."},{"key":"78893_CR8","doi-asserted-by":"publisher","unstructured":"Khan, M. A. H. & Imig, J. D. Antihypertensive Drugs. in Reference Module in Biomedical Sciences. Elsevier (2018), doi: https:\/\/doi.org\/10.1016\/B978-0-12-801238-3.96704-7","DOI":"10.1016\/B978-0-12-801238-3.96704-7"},{"key":"78893_CR9","doi-asserted-by":"publisher","first-page":"36","DOI":"10.5152\/TurkThoracJ.2018.18014","volume":"20","author":"I Yilmaz","year":"2019","unstructured":"Yilmaz, I. Angiotensin-converting enzyme inhibitors induce cough. Turk. Thorac. J. 20, 36\u201342 (2019).","journal-title":"Turk. Thorac. J."},{"key":"78893_CR10","doi-asserted-by":"crossref","unstructured":"Na Takuathung, M. et al. Adverse effects of angiotensin-converting enzyme inhibitors in humans: a systematic review and meta-analysis of 378 randomized controlled trials. IJERPH 19, 8373 (2022).","DOI":"10.3390\/ijerph19148373"},{"key":"78893_CR11","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1172\/JCI39345","volume":"120","author":"CC Wei","year":"2010","unstructured":"Wei, C. C. et al. Mast cell chymase limits the cardiac efficacy of Ang I-converting enzyme inhibitor therapy in rodents. J. Clin. Invest. 120, 1229\u20131239 (2010).","journal-title":"J. Clin. Invest."},{"key":"78893_CR12","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1177\/1753944709334947","volume":"3","author":"F Elijovich","year":"2009","unstructured":"Elijovich, F. & Laffer, C. A role for single-pill triple therapy in hypertension. Ther. Adv. Cardiovasc. Dis. 3, 231\u2013240 (2009).","journal-title":"Ther. Adv. Cardiovasc. Dis."},{"key":"78893_CR13","doi-asserted-by":"publisher","first-page":"920945","DOI":"10.3389\/fnut.2022.920945","volume":"9","author":"D Yang","year":"2022","unstructured":"Yang, D. et al. Formation and inhibition mechanism of novel angiotensin I converting enzyme inhibitory peptides from Chouguiyu. Front. Nutr. 9, 920945 (2022).","journal-title":"Front. Nutr."},{"key":"78893_CR14","doi-asserted-by":"publisher","first-page":"9384","DOI":"10.1021\/acs.jafc.8b02603","volume":"66","author":"B Miralles","year":"2018","unstructured":"Miralles, B., Amigo, L. & Recio, I. Critical review and perspectives on food-derived antihypertensive peptides. J. Agric. Food Chem. 66, 9384\u20139390 (2018).","journal-title":"J. Agric. Food Chem."},{"key":"78893_CR15","doi-asserted-by":"publisher","first-page":"128719","DOI":"10.1016\/j.foodchem.2020.128719","volume":"346","author":"A Kaur","year":"2021","unstructured":"Kaur, A., Kehinde, B. A., Sharma, P., Sharma, D. & Kaur, S. Recently isolated food-derived antihypertensive hydrolysates and peptides: a review. Food Chem. 346, 128719 (2021).","journal-title":"Food Chem."},{"key":"78893_CR16","doi-asserted-by":"publisher","first-page":"316","DOI":"10.3390\/nu9040316","volume":"9","author":"C Daskaya-Dikmen","year":"2017","unstructured":"Daskaya-Dikmen, C., Yucetepe, A., Karbancioglu-Guler, F., Daskaya, H. & Ozcelik, B. Angiotensin-I-converting enzyme (ACE)-inhibitory peptides from plants. Nutrients. 9, 316 (2017).","journal-title":"Nutrients"},{"key":"78893_CR17","doi-asserted-by":"publisher","first-page":"4068","DOI":"10.3390\/ijms22084068","volume":"22","author":"Q Jiang","year":"2021","unstructured":"Jiang, Q. et al. The Antihypertensive effects and potential molecular mechanism of microalgal angiotensin I-converting enzyme inhibitor-like peptides: a mini review. Int. J. Mol. Sci. 22, 4068 (2021).","journal-title":"IJMS"},{"key":"78893_CR18","doi-asserted-by":"publisher","first-page":"383","DOI":"10.21010\/ajtcam.v14i2.39","volume":"14","author":"S Manoharan","year":"2017","unstructured":"Manoharan, S., Shuib, A. S., Abdullah, N. Structural characteristics and antihypertensive effects of angiotensin-I-converting enzyme inhibitory peptides in the renin-angiotensin and kallikrein kinin systems. Afr. J. Tradit Complement. Altern. Med. 14, 383\u2013406 (2017).","journal-title":"Afr. J. Tradit Complement. Altern. Med."},{"key":"78893_CR19","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1002\/bab.1321","volume":"62","author":"T Sornwatana","year":"2015","unstructured":"Sornwatana, T. et al. Terminalia chebula Fruit fruit-derived peptide with angiotensin\u2010I\u2013converting enzyme inhibitory activity. Biotech. App Biochem. 62, 746\u2013753 (2015). Chebulin.","journal-title":"Biotech. App Biochem."},{"key":"78893_CR20","doi-asserted-by":"publisher","first-page":"012041","DOI":"10.1088\/1755-1315\/967\/1\/012041","volume":"967","author":"E Chasanah","year":"2022","unstructured":"Chasanah, E., Martosuyono, P., Budiari, S. & Kurnianto, M. A. Detection of native peptides from Channa striata extract using de novo sequencing. IOP Conf. Ser. : Earth Environ. Sci. 967, 012041 (2022).","journal-title":"IOP Conf. Ser. : Earth Environ. Sci."},{"key":"78893_CR21","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.3892\/ijmm.2017.2941","volume":"39","author":"SY Heo","year":"2017","unstructured":"Heo, S. Y. et al. A heptameric peptide purified from Spirulina sp. gastrointestinal hydrolysate inhibits angiotensin I-converting enzyme- and angiotensin II-induced vascular dysfunction in human endothelial cells. Int. J. Mol. Med. 39, 1072\u20131082 (2017).","journal-title":"Int. J. Mol. Med."},{"key":"78893_CR22","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1186\/1472-6882-13-313","volume":"13","author":"CC Lau","year":"2013","unstructured":"Lau, C. C., Abdullah, N. & Shuib, A. S. Novel angiotensin I-converting enzyme inhibitory peptides derived from an edible mushroom, Pleurotus cystidiosus O.K. Miller identified by LC-MS\/MS. BMC Complement. Altern. Med. 13, 313 (2013).","journal-title":"BMC Complement. Altern. Med."},{"key":"78893_CR23","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3390\/foods11030394","volume":"11","author":"R Wang","year":"2022","unstructured":"Wang, R., Yun, J., Wu, S., Bi, Y. & Zhao, F. Optimisation and characterisation of novel angiotensin-converting enzyme inhibitory peptides prepared by double enzymatic hydrolysis from Agaricus bisporus scraps. Foods. 11, 394 (2022).","journal-title":"Foods"},{"key":"78893_CR24","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1111\/jfbc.12259","volume":"40","author":"T Lafarga","year":"2016","unstructured":"Lafarga, T., Rai, D., O\u2019Connor, K. & Hayes, M. Generation of bioactive hydrolysates and peptides from bovine hemoglobin with in vitro renin, angiotensin-I-converting enzyme and dipeptidyl peptidase-IV inhibitory activities J. Food Biochem. 40, 673\u2013685 (2016).","journal-title":"J. Food Biochem."},{"key":"78893_CR25","doi-asserted-by":"publisher","first-page":"3879","DOI":"10.3390\/molecules26133879","volume":"26","author":"P Mielczarek","year":"2021","unstructured":"Mielczarek, P. et al. Hemorphins\u2014from discovery to functions and pharmacology. Molecules. 26, 3879 (2021).","journal-title":"Molecules"},{"key":"78893_CR26","doi-asserted-by":"publisher","first-page":"14747","DOI":"10.1038\/s41598-019-50619-w","volume":"9","author":"A Ali","year":"2019","unstructured":"Ali, A., Baby, B., Soman, S. S. & Vijayan, R. Molecular insights into the interaction of hemorphin and its targets. Sci. Rep. 9, 14747 (2019).","journal-title":"Sci. Rep."},{"key":"78893_CR27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.biochi.2003.11.001","volume":"86","author":"M Cohen","year":"2004","unstructured":"Cohen, M., Fruitier-Arnaudin, I. & Piot, J. M. Hemorphins: substrates and\/or inhibitors of dipeptidyl peptidase IV. Biochimie. 86, 31\u201337 (2004).","journal-title":"Biochimie"},{"key":"78893_CR28","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3390\/ph14030225","volume":"14","author":"MA Ayoub","year":"2021","unstructured":"Ayoub, M. A. & Vijayan, R. Hemorphins targeting G protein-coupled receptors. Pharmaceuticals. 14, 225 (2021).","journal-title":"Pharmaceuticals"},{"key":"78893_CR29","doi-asserted-by":"publisher","first-page":"108406","DOI":"10.1016\/j.neuropharm.2020.108406","volume":"183","author":"AS Heimann","year":"2021","unstructured":"Heimann, A. S. et al. Hemopressin as a breakthrough for the cannabinoid field. Neuropharmacology. 183, 108406 (2021).","journal-title":"Neuropharmacology"},{"key":"78893_CR30","doi-asserted-by":"publisher","first-page":"20588","DOI":"10.1073\/pnas.0706980105","volume":"104","author":"AS Heimann","year":"2007","unstructured":"Heimann, A. S. et al. Hemopressin is an inverse agonist of CB 1 cannabinoid receptors. Proc. Natl. Acad. Sci. U S A. 104, 20588\u201320593 (2007).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"78893_CR31","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1208\/s12248-010-9217-x","volume":"12","author":"I Gomes","year":"2010","unstructured":"Gomes, I. et al. Hemoglobin-derived peptides as novel type of bioactive signaling molecules. AAPS J. 12, 658\u2013669 (2010).","journal-title":"AAPS J."},{"key":"78893_CR32","doi-asserted-by":"publisher","first-page":"9560","DOI":"10.1038\/s41598-017-09808-8","volume":"7","author":"V Petrucci","year":"2017","unstructured":"Petrucci, V. et al. Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage. Sci. Rep. 7, 9560 (2017).","journal-title":"Sci. Rep."},{"key":"78893_CR33","doi-asserted-by":"publisher","first-page":"36944","DOI":"10.1074\/jbc.M112.382481","volume":"287","author":"M Bauer","year":"2012","unstructured":"Bauer, M. et al. Identification and quantification of a new family of peptide endocannabinoids (pepcans) showing negative allosteric modulation at CB1 receptors. J. Biol. Chem. 287, 36944\u201336967 (2012).","journal-title":"J. Biol. Chem."},{"key":"78893_CR34","doi-asserted-by":"publisher","first-page":"8547","DOI":"10.1074\/jbc.M212030200","volume":"278","author":"V Rioli","year":"2003","unstructured":"Rioli, V. et al. Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme. J. Biol. Chem. 278, 8547\u20138555 (2003).","journal-title":"J. Biol. Chem."},{"key":"78893_CR35","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1038\/nrd1227","volume":"2","author":"KR Acharya","year":"2003","unstructured":"Acharya, K. R., Sturrock, E. D., Riordan, J. F. & Ehlers, M. R. W. ACE revisited: a new target for structure-based drug design. Nat. Rev. Drug Discov. 2, 891\u2013902 (2003).","journal-title":"Nat. Rev. Drug Discov"},{"key":"78893_CR36","volume-title":"Angiotensin-Converting Enzyme Inhibitors (ACEI). (In: StatPearls [Internet]","author":"LL Herman","year":"2023","unstructured":"Herman, L. L. et al. Angiotensin-Converting Enzyme Inhibitors (ACEI). in: StatPearls (StatPearls Publishing, 2023). Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK431051\/"},{"key":"78893_CR37","doi-asserted-by":"publisher","first-page":"e24332","DOI":"10.1002\/pep2.24332","volume":"116","author":"A Alv\u00edz-Amador","year":"2024","unstructured":"Alv\u00edz-Amador, A., Contreras\u2010Puentes, N. & M\u00e1rquez\u2010L\u00e1zaro, J. Bioactive peptides against angiotensin\u2010converting enzyme I: an in silico study. Pept. Sci. 116, e24332 (2024).","journal-title":"Pept. Sci."},{"key":"78893_CR38","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.3168\/jds.2021-21112","volume":"105","author":"S Ningrum","year":"2022","unstructured":"Ningrum, S., Sutrisno, A. & Hsu, J. L. An exploration of angiotensin-converting enzyme (ACE) inhibitory peptides derived from gastrointestinal protease hydrolysate of milk using a modified bioassay-guided fractionation approach coupled with in silico analysis. J. Dairy Sci. 105, 1913\u20131928 (2022).","journal-title":"J. Dairy Sci."},{"key":"78893_CR39","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.biomed.2012.06.005","volume":"2","author":"CL Jao","year":"2012","unstructured":"Jao, C. L., Huang, S. L. & Hsu, K. C. Angiotensin I-converting enzyme inhibitory peptides: inhibition mode, bioavailability, and antihypertensive effects. BioMedicine. 2, 130\u2013136 (2012).","journal-title":"BioMedicine"},{"key":"78893_CR40","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nature01370","volume":"421","author":"R Natesh","year":"2003","unstructured":"Natesh, R., Schwager, S. L. U., Sturrock, E. D. & Acharya, K. R. Crystal structure of the human angiotensin-converting enzyme\u2013lisinopril complex. Nature. 421, 551\u2013554 (2003).","journal-title":"Nature"},{"key":"78893_CR41","doi-asserted-by":"publisher","first-page":"124620","DOI":"10.1016\/j.seppur.2023.124620","volume":"324","author":"S Yue","year":"2023","unstructured":"Yue, S. et al. Highly selective and pH responsive adsorption of ZIF-8 for angiotensin-converting enzyme (ACE) inhibitory active peptides and its mechanism. Sep. Purif. Technol. 324, 124620 (2023).","journal-title":"Sep. Purif. Technol."},{"key":"78893_CR42","doi-asserted-by":"publisher","first-page":"110161","DOI":"10.1016\/j.foodres.2021.110161","volume":"141","author":"S Sanjukta","year":"2021","unstructured":"Sanjukta, S. et al. Production, characterization and molecular docking of antioxidant peptides from peptidome of kinema fermented with proteolytic Bacillus spp. Food Res. Int. 141, 110161 (2021).","journal-title":"Food Res. Int."},{"key":"78893_CR43","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1111\/1541-4337.12051","volume":"13","author":"A Iwaniak","year":"2014","unstructured":"Iwaniak, A., Minkiewicz, P., Darewicz, M., Food-originating ACE inhibitors, including antihypertensive peptides, as preventive food components in blood pressure reduction. Comp. Rev. Food Sci. Food Safe. 13, 114\u2013134 (2014).","journal-title":"Comp. Rev. Food Sci. Food Safe"},{"key":"78893_CR44","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1021\/jf051263l","volume":"54","author":"J Wu","year":"2006","unstructured":"Wu, J., Aluko, R. E. & Nakai, S. Structural requirements of angiotensin I-converting enzyme inhibitory peptides: quantitative structure\u2009\u2013\u2009activity relationship study of di- and tripeptides. J. Agric. Food Chem. 54, 732\u2013738 (2006).","journal-title":"J. Agric. Food Chem."},{"key":"78893_CR45","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/0162-0134(85)85002-9","volume":"24","author":"P B\u00fcnning","year":"1985","unstructured":"B\u00fcnning, P. The functional role of zinc in angiotensin converting enzyme: implications for the enzyme mechanism. J. Inorg. Biochem. 24, 183\u2013198 (1985).","journal-title":"J. Inorg. Biochem."},{"key":"78893_CR46","doi-asserted-by":"publisher","first-page":"968104","DOI":"10.3389\/fphar.2022.968104","volume":"13","author":"W Zheng","year":"2022","unstructured":"Zheng, W. et al. Small molecule angiotensin converting enzyme inhibitors: a medicinal chemistry perspective. Front. Pharmacol. 13, 968104 (2022).","journal-title":"Front. Pharmacol."},{"key":"78893_CR47","doi-asserted-by":"publisher","first-page":"2643","DOI":"10.3389\/fmicb.2019.02643","volume":"10","author":"J Li","year":"2019","unstructured":"Li, J. et al. Novel angiotensin-converting enzyme-inhibitory peptides from fermented bovine milk started by Lactobacillus helveticus KLDS.31 and Lactobacillus casei KLDS.105: purification, identification, and Interaction mechanisms. Front. Microbiol. 10, 2643 (2019).","journal-title":"Front. Microbiol."},{"key":"78893_CR48","first-page":"101211","volume":"21","author":"G Wei","year":"2024","unstructured":"Wei, G. et al. Identification, structural characterization, and molecular dynamic simulation of ACE inhibitory peptides in whey hydrolysates from Chinese Rushan cheese by-product. Food Chemistry: X. 21, 101211 (2024).","journal-title":"Food Chemistry: X"},{"key":"78893_CR49","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3390\/md16080271","volume":"16","author":"J Li","year":"2018","unstructured":"Li, J. et al. 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, 271 (2018).","journal-title":"Mar. Drugs"},{"key":"78893_CR50","unstructured":"Schr\u00f6dinger, L. L. C. New York, NY, USA."},{"key":"78893_CR51","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","volume":"27","author":"G Madhavi Sastry","year":"2013","unstructured":"Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R. & Sherman, W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aided Mol. Des. 27, 221\u2013234 (2013).","journal-title":"J. Comput. Aided Mol. Des."},{"key":"78893_CR52","unstructured":"Schr\u00f6dinger Release 2022-4. Protein Preparation Wizard; Epik, Schr\u00f6dinger, LLC: New York, NY, USA, (2022)."},{"key":"78893_CR53","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/gb-2003-4-8-225","volume":"4","author":"JF Riordan","year":"2003","unstructured":"Riordan, J. F. Angiotensin-I-converting enzyme and its relatives. Genome Biol. 4, 225 (2003).","journal-title":"Genome Biol."},{"key":"78893_CR54","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","volume":"47","author":"RA Friesner","year":"2004","unstructured":"Friesner, R. A. et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 47, 1739\u20131749 (2004).","journal-title":"J. Med. Chem."},{"key":"78893_CR55","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1021\/jm030644s","volume":"47","author":"TA Halgren","year":"2004","unstructured":"Halgren, T. A. et al. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem. 47, 1750\u20131759 (2004).","journal-title":"J. Med. Chem."},{"key":"78893_CR56","doi-asserted-by":"publisher","first-page":"6177","DOI":"10.1021\/jm051256o","volume":"49","author":"RA Friesner","year":"2006","unstructured":"Friesner, R. A. et al. Extra precision Glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein\u2009\u2013\u2009ligand complexes. J. Med. Chem. 49, 6177\u20136196 (2006).","journal-title":"J. Med. Chem."},{"key":"78893_CR57","unstructured":"Schr\u00f6dinger Release 2020-4: Desmond Molecular Dynamics System & Shaw Research, D. E. New York, NY, ; Maestro-Desmond Interoperability Tools, Schr\u00f6dinger: New York, NY, USA, 2020. (2021)."},{"key":"78893_CR58","doi-asserted-by":"publisher","unstructured":"Bowers, K. J. et al. IEEE, Tampa, FL,. Scalable algorithms for molecular dynamics simulations on commodity clusters. in ACM\/IEEE SC 2006 Conference (SC\u201906) 43\u201343 doi: (2006). https:\/\/doi.org\/10.1109\/SC.2006.54","DOI":"10.1109\/SC.2006.54"},{"key":"78893_CR59","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1063\/1.470117","volume":"103","author":"U Essmann","year":"1995","unstructured":"Essmann, U. et al. A smooth particle mesh Ewald method. J. Chem. Phys. 103, 8577\u20138593 (1995).","journal-title":"J. Chem. Phys."},{"key":"78893_CR60","doi-asserted-by":"publisher","first-page":"4177","DOI":"10.1063\/1.467468","volume":"101","author":"GJ Martyna","year":"1994","unstructured":"Martyna, G. J., Tobias, D. J. & Klein, M. L. Constant pressure molecular dynamics algorithms. J. Chem. Phys. 101, 4177\u20134189 (1994).","journal-title":"J. Chem. Phys."},{"key":"78893_CR61","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1063\/1.463940","volume":"97","author":"GJ Martyna","year":"1992","unstructured":"Martyna, G. J., Klein, M. L. & Tuckerman, M. Nos\u00e9\u2013Hoover chains: the canonical ensemble via continuous dynamics. J. Chem. Phys. 97, 2635\u20132643 (1992).","journal-title":"J. Chem. Phys."},{"key":"78893_CR62","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1063\/1.463137","volume":"97","author":"M Tuckerman","year":"1992","unstructured":"Tuckerman, M., Berne, B. J. & Martyna, G. J. Reversible multiple time scale molecular dynamics. J. Chem. Phys. 97, 1990\u20132001 (1992).","journal-title":"J. Chem. Phys."},{"key":"78893_CR63","doi-asserted-by":"crossref","unstructured":"Kr\u00e4utler, V., Van Gunsteren, W.F., H\u00fcnenberger, P.H. A fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations. J. Comput. Chem., 22, 501\u2013508 (2001).","DOI":"10.1002\/1096-987X(20010415)22:5<501::AID-JCC1021>3.0.CO;2-V"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-78893-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-78893-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-78893-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T10:04:41Z","timestamp":1732097081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-78893-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["78893"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-78893-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]},"assertion":[{"value":"11 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"R.V. is an editorial board member of Scientific Reports. The other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"28726"}}