DNA encodes genetic instructions relevant to the development and functioning of living organisms and viruses. One of the primary regulators of gene transcription is DNA methylation. DNA methylation occurs at specific sites in DNA, referred to as genetic hot spots or CpG islands. However, aberrant DNA methylation patterns such as hypermethylation and hypomethylation have been recognized in variety of human malignancies. As a result, the process has become one of the most thoroughly investigated epigenetic modifications in mammals. Experimental evidence shows cancer-specific differential DNA-methylated regions correspond to the loss of sharply defined methylation boundaries at CpG islands. Developing effective cancer therapeutic requires a proper understanding of gene silencing and gene expression associated with methylation and demethylation. However, the relevance of methylation or demethylation to cancer is far from being well explained. Interactions between nucleic acids and graphene were studied as an approach to study the interaction between proteins and methylated DNA. Nucleic acids have shown a planar orientation on graphene due to the influence of π−π interactions. Dispersion-corrected density-functional calculations demonstrate that nucleotide base-oriented conformations transfer more charge than phosphate-oriented conformations. The constructed double-strand DNA sequences contain only Cytosine and Guanine in the double-strands for simplicity. Constructed CpG islands are the localities where methyl groups attach to cytosine. The constructed structures vary from an unmethylated DNA (0% or hypomethylated), to 10% methylated DNA, and to 20-100% (hypermethylated) DNAs. Study shows that the increasing methyl concentration decreases the binding energy with an increase of the average distance between the strands. Consequently, normal regulation of gene can be disrupted. Energy gap between filled and empty orbital in the methylated double strand DNA increases with increasing concentration of methyl group in the DNA. Results indicate that abnormal DNA methylation is affecting the electronic structure of the DNA and hence effecting the proper bio-functioning of vertebrates.

Multi-scale modeling of deoxyribonucleic acid (DNA) methylation and a computational study of orbital interaction, band gap and binding energies associated with the process

ACS Fall 2021

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