Study of pH influence on the stability of 175th codon of P53 genes by computational and modeling methods

P53 tumor suppressor gene, also known as “genome guardian” is mutated in more than half of all kind of cancers. In this study we have investigated the controls of environmental pH for P53 gene mutation in point of specific sequence which is prone to mutagenesis. The most probable cancerous mutations occur as point mutations in exons 5-8 of P53 gene. The 175th codon of P53 is the third most mutated codon in this gene. By experimental research, it is revealed that acidic pH raised the rate of cancer and mutation in 175 CGC codon of P53 gene. It to some extent is due to protonation of this three nucleotide codon. Mutation in this codon changes the encoding amino acid and subsequently produces a protein which has oncogenic features instead of tumor suppressor characteristics of original p53 protein. In current study, we perform investigation on the impact of protonation on stability of codon 175CGC in this gene. We used HyperChem software for answering to our mentioned goal above. Our results suggested a reliable answer about the effect of protonation on mentioned codon and its stability. From theoretical point of view, acidity can decrease the instability of this specific codon. Along with the experimental investigations, our results can to some extent elaborate acidic pH competency to cause mutation.