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Both the TOPII\u03b1 and TOPII\u03b2 isoforms are considered herein, with doxorubicin and berubicin, two TOPII poisons, as the anthracyclines of interest. From a thermodynamic point of view, we find that all complexes investigated exhibit more negative standard binding Gibbs energies than berubicin\u2013DNA intercalation complexes, showing that the presence of TOPII\u03b1 or TOPII\u03b2 further stabilizes the complexes. The berubicin\u2013DNA\u2013TOPII\u03b1 complex exhibits the most negative standard binding Gibbs energy. Therefore, berubicin shows a preference for TOPII\u03b1 over TOPII\u03b2; the former is highly expressed in proliferating cells, including cancer cells, whereas the latter is expressed ubiquitously. From a nanoscopic point of view, our rigorous in silico approach sheds light on the interactions of the two anthracyclines with both DNA and TOPII and on how they contribute to the hindering of religation. Moreover, this study provides a detailed comparison between doxorubicin and berubicin in terms of relevant properties, such as contact numbers, hydrogen bonds, selected distances, and solvent-accessible surface areas.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01823","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:04:28Z","timestamp":1789470268000},"page":"12060-12074","source":"Crossref","is-referenced-by-count":0,"title":["Binding of Anthracyclines\nWithin DNA\u2013Topoisomerase\n\u0399\u0399 Cleavage Complexes: Thermodynamics and Interactions"],"prefix":"10.1021","volume":"66","author":[{"given":"Georgios","family":"Mikaelian","sequence":"first","affiliation":[{"name":"National Technical University of Athens (NTUA) , , 9 Heroon Polytechniou Street, Zografou Campus , ,","place":["Athens, Greece, GR-15780"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8607-9965","authenticated-orcid":true,"given":"Haralambos","family":"Sarimveis","sequence":"additional","affiliation":[{"name":"National Technical University of Athens (NTUA) , , 9 Heroon Polytechniou Street, Zografou Campus , ,","place":["Athens, Greece, GR-15780"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doros N.","family":"Theodorou","sequence":"additional","affiliation":[{"name":"National Technical University of Athens (NTUA) , , 9 Heroon Polytechniou Street, Zografou Campus , ,","place":["Athens, Greece, GR-15780"]},{"name":"Academy of Athens , 28 Panepistimiou Street , ,","place":["Athens, Greece, GR-10679"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2283-7085","authenticated-orcid":true,"given":"Grigorios","family":"Megariotis","sequence":"additional","affiliation":[{"name":"National Technical University of Athens (NTUA) , , 9 Heroon Polytechniou Street, Zografou Campus , ,","place":["Athens, Greece, GR-15780"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"issue":"2","key":"2026092810073865100_cit1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1124\/pr.56.2.6","article-title":"Anthracyclines:\nmolecular advances and pharmacologic developments in antitumor activity\nand cardiotoxicity","volume":"56","author":"Minotti","year":"2004","journal-title":"Pharmacol. 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