Biophysical Society Thematic Meeting| Lima 2019

Revisiting the Central Dogma of Molecular Biology at the Single-Molecule Level

Poster Abstracts

42-POS Board 42 MODELING METHYLATION IN STACKED GPC-CPG DNA SEQUENCE CONSIDERING BACKBONES Cesaré Ovando-Vázquez 1 ; Daniel Salgado-Blanco 1 ; Florentino López-Urías 2 ; 1 CONACYT , CNS-IPICYT, San Luis Potosí, Mexico 2 IPICYT, DMAV, San Luis Potosí, Mexico The incorporation of a methyl group to DNA nucleotides (methylation) is a well know epigenetic regulation phenomena. Methylation can result in gene silencing. The methylation (m) of cytosine base (C) at GpC sequence site, was investigated using first-principles density functional theory calculations to elucidate the changes of the electronic structure. We investigated the bare G-C and G-Cm Watson-Crick base pairs electronic properties. Also, we incorporated a sugar- phosphate to these systems to generate the pG-pC and pG-pCm systems. Beyond these, we investigated the stacked GpC-CpG, GpC-mCpG and GpCm-mCpG systems. Methylated stacked base pairs were analyzed and compared with the non-methylated case (GpC-CpG). The structures were relaxed using conjugated gradient method. We present results for the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) wave functions, charge Mulliken population, and dipole moments. We demonstrate that the backbone or the deoxyribose-phosphate chain plays a crucial role in the spatial distribution of HOMO and LUMO wave functions in the stacked systems. Cytosine methylation results in electronic structure changes, suggesting reactivity modulation affecting the protein binding to methylated DNA, such as transcription factors or histones. Also, dipole moment modification in the studied systems could favor specific protein-DNA interactions due to the methyl group non-polarity, producing water fear DNA regions. Cytosine methylation on the GpC-CpG system results in a stabilization effect. These observations could help explaining the quantum nature of methylation gene silencing.

79