Atomistic Insights Into Interaction of Doxorubicin With DNA: From Duplex to Nucleosome
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F25%3A00605573" target="_blank" >RIV/68081707:_____/25:00605573 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/61989592:15640/25:73629836 RIV/61989100:27740/25:10256709
Výsledek na webu
<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70035" target="_blank" >https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70035</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/jcc.70035" target="_blank" >10.1002/jcc.70035</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Atomistic Insights Into Interaction of Doxorubicin With DNA: From Duplex to Nucleosome
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Atomistic Insights Into Interaction of Doxorubicin With DNA: From Duplex to Nucleosome
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10401 - Organic chemistry
Návaznosti výsledku
Projekt
<a href="/cs/project/EH22_008%2F0004587" target="_blank" >EH22_008/0004587: Technologie za hranicí nanosvěta</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2025
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Computational Chemistry
ISSN
0192-8651
e-ISSN
1096-987X
Svazek periodika
46
Číslo periodika v rámci svazku
3
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
12
Strana od-do
e70035
Kód UT WoS článku
001406650800001
EID výsledku v databázi Scopus
2-s2.0-85216255318