Berlin 2024 – scientific programme
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BP: Fachverband Biologische Physik
BP 26: Biopolymers, Biomaterials and Bioinspired Functional Materials (joint session CPP/BP)
BP 26.10: Talk
Thursday, March 21, 2024, 12:15–12:30, H 0111
A Computational Investigation into the Oxidation of Cytosine Epigenetic Modifications — •Vasilii Korotenko1 and Hendrik Zipse2 — 1Forschungszentrum Jülich, IEK-9 — 2LMU München, Fakultät für Chemie und Pharmazie
Studying the (aut)oxidation of 5-methylcytosine (5mC) is crucial for understanding the dynamic control of DNA methylation - a pivotal epigenetic modification linked to gene expression, cellular differentiation, and disease development. In this work, the oxidizing properties of oxygen-centered radicals and the reducing properties of epigenetically modified cytosines were studied. The O-H bond dissociation energies BDE(O-H) were calculated for various alcohols using selected theoretical methods. BDE(C-H) and pKa values have been calculated for various oxidation product of 5mC. Special attention was paid to the equilibrium of the hydration reaction of 5-formylcytosine (5fC), because the corresponding hydrate product can be very easily oxidized. All this together allowed us to propose and thermodynamically evaluate the mechanism of the 5mC (aut)oxidation reaction. The (aut)oxidation of 5mC is unlikely to occur through initiation by triplet dioxygen or through unimolecular decomposition of hydroperoxides. In the proposal mechanism, neural molecules react with free radicals, transferring hydrogen atoms to create products with higher BDE values. The thermodynamics of the presented mechanism agrees with the experimental kinetics. We assume that the protonation (pH < 7) of oxidizable nucleic acids inhibits the (aut)oxidation process by increasing the BDE(C-H) values.
Keywords: epigenetics; radicals; free energy; oxidation; computational chemistry