Doxorubicin (DOX) is a widely used chemotherapeutic agent known for intercalating into DNA. However, the exact modes of DOX interactions with various DNA structures remain unclear. Using molecular dynamics (MD) simulations, we explored DOX interactions with DNA duplexes (dsDNA), G-quadruplex, and nucleosome. DOX predominantly stacks on terminal bases of dsDNA and occasionally binds into its minor groove. In the G-quadruplex, DOX stacks on planar tetrads but does not spontaneously intercalate into these structures. Potential of mean force calculations indicate that while intercalation is the most energetically favorable interaction mode for DOX in dsDNA, the process requires overcoming a significant energy barrier. In contrast, DOX spontaneously intercalates into bent nucleosomal DNA, due to the increased torsional stress. This preferential intercalation of DOX into regions with higher torsional stress provides new insights into its mechanism of action and underscores the importance of DNA tertiary and quaternary structures in therapies utilizing DNA intercalation.

• Klíčová slova
• DNA, G‐quadruplex, MD simulations, doxorubicin intercalation, intercalation, nucleosome,
• MeSH
• antibiotika antitumorózní chemie   farmakologie   MeSH
• DNA * chemie   MeSH
• doxorubicin * chemie   farmakologie   MeSH
• G-kvadruplexy MeSH
• interkalátory chemie   farmakologie   MeSH
• konformace nukleové kyseliny MeSH
• nukleozomy * chemie   metabolismus   MeSH
• simulace molekulární dynamiky * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibiotika antitumorózní MeSH
• DNA * MeSH
• doxorubicin * MeSH
• interkalátory MeSH
• nukleozomy * MeSH