{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:52:29Z","timestamp":1791895949498,"version":"4.3.4"},"reference-count":79,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Protein\u2010bound uremic toxins (PBUTs) such as 4\u2010ethylphenyl sulfate (4\u2010EPS) challenge kidney failure management due to strong binding to human serum albumin (HSA), thus\u00a0limiting dialysis clearance. This study examined 4\u2010EPS\u2013HSA interactions using saturation transfer difference nuclear magnetic resonance spectroscopy (STD\u2010NMR), isothermal titration calorimetry (ITC), in silico analysis via molecular docking, molecular dynamics (MD), and molecular mechanics Generalized Born surface area (MM\/GBSA) simulations. STD\u2010NMR qualitatively showed competitive binding with the site\u2010specific ligands, warfarin and ibuprofen, indicating interaction with both Sudlow Sites I and II; competitive ITC results also showed competition between these molecules. ITC analysis using a two\u2010component model indicated two distinct binding interactions with association constants\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>a1<\/jats:sub>\n                    \u2009=\u20096.62\u2009\u00d7\u200910\n                    <jats:sup>5<\/jats:sup>\n                    \u2009M\n                    <jats:sup>\u22121<\/jats:sup>\n                    (entropically unfavorable) and\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>a2<\/jats:sub>\n                    \u2009=\u20092.71\u2009\u00d7\u200910\n                    <jats:sup>4<\/jats:sup>\n                    \u2009M\n                    <jats:sup>\u22121<\/jats:sup>\n                    (enthalpically favorable), respectively. Docking models were used to analyze representative binding poses at Sudlow Sites I and II, while MD revealed hydrophobic stabilization at Site I and polar interactions at Site II. MM\/GBSA per\u2010residue decomposition identified key stabilizing residues. Circular dichroism measurements showed that the observed binding effects are not accompanied by gross protein unfolding. Comparisons with other PBUTs, including indoxyl sulfate and\n                    <jats:italic>p<\/jats:italic>\n                    \u2010cresyl sulfate, indicated the role of electrostatic and hydrophobic forces involved in binding. These findings advance understanding of PBUT\u2013HSA interactions and inform strategies for improved toxin removal in kidney failure treatments.\n                  <\/jats:p>","DOI":"10.1002\/pro.70755","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:02:58Z","timestamp":1786532578000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["4\u2010Ethyl phenyl sulfate binding to human serum albumin"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9677-7312","authenticated-orcid":false,"given":"Vida Dehghan","family":"Niestanak","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Alberta  Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4506-5957","authenticated-orcid":false,"given":"Jacopo","family":"Zattoni","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Alberta  Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0255-159X","authenticated-orcid":false,"given":"Ryan T.","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Alberta  Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0846-3187","authenticated-orcid":false,"given":"Marcello","family":"Tonelli","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3532-4956","authenticated-orcid":false,"given":"Maral","family":"Aminpour","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Alberta  Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3162-3545","authenticated-orcid":false,"given":"Larry D.","family":"Unsworth","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering University of Alberta  Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16453"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28093724"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00249-011-0749-5"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10973-013-3067-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8630-9_4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1091"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-013-6931-0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(74)80645-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.3c01153"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20290"},{"key":"e_1_2_8_13_1","unstructured":"Chemical Book.4\u2010Ethylphenol(123\u201007\u20109)1H NMR. n.d.\u2010a.https:\/\/www.chemicalbook.com\/SpectrumEN_123-07-9_1HNMR.htm. 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