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Abstract

DNA methylation occurring on the O6 position of guanine has been linked to the formation of cancer. DNA complexes with O6-methylated guanine have been studied experimentally, yet questions remain concerning the carcinogenic properties of O6-methylguanine. This present research explored the interaction between O6-methylguanine and its potential nucleobase pairs of cytosine and adenine in hopes of elucidating the mutagenic characteristics of O6-methylguanine. A variety of computational methods including Density Functional Theory (DFT), Symmetry Adapted Perturbation Theory (SAPT), Noncovalent Interaction (NCI) analysis, and Natural Bond Orbital (NBO) analysis were employed to comprehensively probe this system.

Upon analysis of these results, it was observed that O6-methylation causes a significant decrease in the interaction energy between the base pairs when compared to the canonical guanine-cytosine base pair. Methylated guanine also has a higher likelihood of mispairing with a only a modest preference for pairing with cytosine over thymine. Furthermore, when mispaired with thymine, the complex loses a coplanar configuration, leading to instability within the DNA complex. This research may be leveraged to understand how cancer is formed and minimize the associated risks, which would spread God’s love by making the world a healthier place. Moreover, the wisdom of God is revealed to the world by studying the complex and robust mechanisms involved with DNA and the maintenance of life.

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