2026-04-17T06:38:25Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1759442025-11-19T10:41:28Zcom_2072_1057col_2072_478815col_2072_478917

00925njm 22002777a 4500 dc Corbella Morató, Marina author Voityuk, Alexander A. author Curutchet Barat, Carles E. author 2021-04-01T05:26:57Z 2021-04-01T05:26:57Z 2015-09-02 2021-04-01T05:26:58Z Different mutagenic effects are generated by DNA oxidation that implies the formation of radical cation states (so-called holes) on purine nucleobases. The interaction of DNA with proteins may protect DNA from oxidative damage owing to hole transfer (HT) from the stack to aromatic amino acids. However, how protein binding affects HT dynamics in DNA is still poorly understood. Here, we report a computational study of HT in DNA complexes with methyltransferase HhaI with the aim of elucidating the molecular factors that explain why long-range DNA HT is inhibited when the glutamine residue inserted in the double helix is mutated into a tryptophan. We combine molecular dynamics, quantum chemistry, and kinetic Monte Carlo simulations and find that protein binding stabilizes the energies of the guanine radical cation states and significantly impacts the corresponding electronic couplings, thus determining the observed behavior, whereas the formation of a tryptophan radical leads to less efficient HT. Transferència d'energia Transferència de càrrega ADN Reparació de l'ADN Complexitat computacional Energy transfer Charge transfer DNA DNA repair Computational complexity Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes