DNA methylation, a biological process by which methyl groups are added to the DNA molecule, typically acts to repress gene transcription. It is associated with several processes including carcinogenesis, thus serving as a universal cancer biomarker. Nanomaterials have been proposed as a promising candidate for methylated DNA detection. Revealing unique interactions between methylated DNA and nanomaterials such as graphene oxide (GO) can make provision for a universal cancer screening. To gain insights into the molecular-level interactions, molecular dynamics (MD) simulation and density functional theory (DFT) calculation have been provided for observing the interactions at the macro- and micro-level. Based upon the MD simulation, different adsorption of methylated and unmethylated DNA on the GO were represented by contacting surface area (CSA) which depends on surrounding conditions (in water or MgCl2 solution). In water, the CSA of the methylated and unmethylated ssDNA were ~ 13 nm2 and ~ 5 nm2, respectively, representing more preferable adsorption on the GO for the methylated ssDNA. In the presence of divalent ions (Mg2+), the CSA of both cases were ~ 8 nm2, suggesting that there was no different adsorption in the saline solution. To reveal the electrical property of GO covered by either methylated or unmethylated DNA, its electronic structure was investigated by the DFT calculation. The energy gap of the pristine graphene (pG) and GO adsorbed by 5-methylcytosine (5mC) were 1.6 and 12.9 meV, respectively, while cytosine adsorption resulted in lower energy gaps (1.2 meV for pG and 9.5 meV for GO). The remarkable difference in the electronic structure of the GO in the presence of methylated or unmethylated DNA, resulting in different electrical conductivity, will pave the way for designing the novel sensing kit, based on GO, for universal cancer screening.

Effects of DNA methylation on the interactions between DNA and graphene oxide nanosheet: In silico study for a universal cancer screening kit

ACS Spring Meeting 2021

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