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Radiotoxic An are routinely involved in the nuclear fuel cycle and the possibility of their accidental exposure cannot be ruled out. Understanding An interaction with sTf assumes a greater significance for the development of safe and efficacious chelators for their removal from the blood stream. Here we report several 100\u2009ns equilibrium MD simulations of Cm(III)\u2010 and Th(IV)\u2010loaded sTf at various protonation states of the protein to explore the possibility of the two An ions release and speciation. The results demonstrate variation in protonation state of dilysine pair (K206 and K296) and the tyrosine (Y188) residue is necessary for the opening of Cm(III)\u2010bound protein and the release of the ion. For the tetravalent thorium, protonation of dilysine pair suffices to cause conformational changes of protein. However, in none of the protonation states, Th(IV) releases from sTf because of its strong electrostatic interaction with D63 in the first shell of the sTf binding cleft. Analysis of hydrogen bond, water bridge, and the evaluation of potential of mean forces of the An ions' release from sTf, substantiate the differential behavior of Cm(III) and Th(IV) at endosomal pH. The results provide insight in the regulation of Cm(III) and Th(IV) bioavailability that may prove useful for effective design of their decorporating agents and as well may help the future design of radiotherapy based on tetravalent ions.<\/jats:p>","DOI":"10.1002\/prot.26006","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T18:23:42Z","timestamp":1610303022000},"page":"193-206","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>MD<\/scp> simulation reveals differential binding of Cm(<scp>III<\/scp>) and Th(<scp>IV<\/scp>) with serum transferrin at acidic <scp>pH<\/scp>"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-1586","authenticated-orcid":false,"given":"Lokpati","family":"Mishra","sequence":"first","affiliation":[{"name":"Radiation Safety Systems Division Bhabha Atomic Research Centre  Mumbai India"},{"name":"Department of Chemical Sciences Homi Bhabha National Institute  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahesh","family":"Sundararajan","sequence":"additional","affiliation":[{"name":"Theoretical Chemistry Section Bhabha Atomic Research Centre  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9359-6303","authenticated-orcid":false,"given":"Tusar","family":"Bandyopadhyay","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences Homi Bhabha National Institute  Mumbai India"},{"name":"Theoretical Chemistry Section Bhabha Atomic Research Centre  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0883-2897(87)90157-7"},{"key":"e_1_2_8_3_1","first-page":"271","article-title":"Binding of f\u2010elements to the iron\u2010transport protein transferrin","volume":"28","author":"Taylor D","year":"1991","journal-title":"Eur J Solid State Inorg Chem"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-8388(98)00014-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200901209"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3DT53371A"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4NJ01877J"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4DT03403A"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1021\/tx900184r","article-title":"Structural insights into the binding of uranyl with human serum protein apotransferrin structure and spectra of protein\u2010uranyl interactions","volume":"22","author":"Benavides\u2010Garcia MG","year":"2009","journal-title":"Chem Res Toxicol"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553008114551401"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr980430w"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1093\/rpd\/ncy004","article-title":"Comparing lungs, liver and knee measurement geometries at various times post inhalation of 239Pu and 241Am","volume":"181","author":"Mishra L","year":"2018","journal-title":"Radiat Prot Dosim"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.apradiso.2015.06.012","article-title":"Applying a low energy HPGe detector gamma ray spectrometric technique for the evaluation of Pu\/am ratio in biological samples","volume":"104","author":"Singh IS","year":"2015","journal-title":"Appl Radiat Isot"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2006.06.011"},{"key":"e_1_2_8_15_1","first-page":"362","article-title":"The binding and transport of alternative metals by transferrin","volume":"2012","author":"Vincent JB","year":"1820","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_8_16_1","first-page":"237","article-title":"Coord. 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