Reactive Molecular Dynamics Simulation of the Structural Damages of the B-DNA Induced by the Oxidation/Nitration of Guanine

ME Izadi and H Sabzyan, JOURNAL OF PHYSICAL CHEMISTRY B, 126, 10347-10359 (2022).

DOI: 10.1021/acs.jpcb.2c05151

Reactive molecular dynamics simulations (RMD) have been carried out to investigate structural alterations of the dodecamer double-strand B-DNA due to the oxidation/nitration modifications introduced to its guanine bases, including 8-oxoguanine, 8-nitroguanine, and 5-guanidino-4-nitroirnidazole, considering two distribution patterns. These modifications may arise in the case of cancer treatment using oxidative/nitrosative reactive nitrogen species as anticancer agents. Results show that these mutations affect structural characteristics of the B-DNA dodecamer in the order 8-nitroguanine > 5-guanidino-4-nitroimidazole >> 8-oxoguanine. For instance, the base- pair per turn for these modified B-DNA are changed respectively to 9.79, 10.88 and 10.58 from 10.51 in the native defect-free B-DNA, which is compatible with the experimental value of 10.10. In addition, these mutations allow more water molecules to diffuse into the dodecamer structure and consequently increase the possibility of the penetration of reactive and nonreactive species toward constituting nucleic base- pairs. The largest variation of the B-DNA structure is observed for the mutated B-DNA with 8-nitroguanine modifications applied to its separated CG base-pairs along the dodecamer chain. The structural changes introduced by these nitro-/oxo-modified guanine bases can be considered as a critical step in the damage of the DNA structure and alterations of its function.

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