DFT and QM/MM Study of interactions of NSAIDs and Beta‐Blockers with DNA DOI Open Access
I. Çetin Öztürk, Toomas Tamm, Armağan Kınal

и другие.

ChemistrySelect, Год журнала: 2025, Номер 10(10)

Опубликована: Март 1, 2025

Abstract This study investigated the interactions of widely used NSAIDs and beta‐blocker drugs with DNA using quantum mechanics aim understanding applicability QM models to large systems. Using ωB97X‐D/6–31+G(d,p) DFT method, we analyzed drug‐nucleobase binding found that oxaprozin mefenamic acid significantly distorted nucleobase pair geometries, displacing thymine in adenine–thymine pairs guanine cytosine–guanine pairs. These distortions suggest a potential mechanism underlying adverse effects these drugs. To extend our model, employed QM/MM simulations observe between fragments an explicit solvent environment. Simulations revealed primarily interacted cytosine nucleobases, disrupting hydrogen bonds indicating intercalative mode. Single‐point energy calculations validated results, showing agreement while highlighting need for comprehensive fully evaluate drug‐DNA interactions. Our findings demonstrate can effectively predict larger systems, providing insights into drug mechanisms side effects.

Язык: Английский

DFT and QM/MM Study of interactions of NSAIDs and Beta‐Blockers with DNA DOI Open Access
I. Çetin Öztürk, Toomas Tamm, Armağan Kınal

и другие.

ChemistrySelect, Год журнала: 2025, Номер 10(10)

Опубликована: Март 1, 2025

Abstract This study investigated the interactions of widely used NSAIDs and beta‐blocker drugs with DNA using quantum mechanics aim understanding applicability QM models to large systems. Using ωB97X‐D/6–31+G(d,p) DFT method, we analyzed drug‐nucleobase binding found that oxaprozin mefenamic acid significantly distorted nucleobase pair geometries, displacing thymine in adenine–thymine pairs guanine cytosine–guanine pairs. These distortions suggest a potential mechanism underlying adverse effects these drugs. To extend our model, employed QM/MM simulations observe between fragments an explicit solvent environment. Simulations revealed primarily interacted cytosine nucleobases, disrupting hydrogen bonds indicating intercalative mode. Single‐point energy calculations validated results, showing agreement while highlighting need for comprehensive fully evaluate drug‐DNA interactions. Our findings demonstrate can effectively predict larger systems, providing insights into drug mechanisms side effects.

Язык: Английский

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