Computational simulations and experimental validation of structure- physicochemical properties of pristine and functionalized graphene: Implications for adverse effects on p53 mediated DNA damage response

Recent reports indicated DNA damaging potential of few-layer graphene in human cell systems. Here, we used computational technique to understand the interaction of both pristine (pG) or carboxyl functionalized graphene (fG) of different sizes (1, 6, and 10 nm) with an important DNA repair protein p53. The molecular docking study revealed strong interaction between pG and DNA binding domains (DBD) of p53 with binding free energies (BE) varying from −12.0 (1 nm) to −34 (6 nm) kcal/mol, while fG showed relatively less interaction with BE varying from −6.7 (1 nm) to −11.1 (6 nm) kcal/mol. Most importantly, pG or fG bound p53-DBDs could not bind to DNA. Further, microarray analysis of human primary endothelial cells revealed graphene intervention on DNA damage and its structure-properties effect using comet assay studies. Thus, computational and experimental results revealed the structure-physicochemical property dependent adverse effects of graphene in DNA repair protein p53.