Computational Inverstigation of the Effects of Post Translational Modifications and Cancer Mutation on PARP-2

Proteins found in the human body carry out specific functions necessary for the operation of the body. Their specific mechanisms are dictated by the amino acid residues of which they are constructed. Both the type and order of the residues affects the folding, motion, and functions of the protein. Any change in the makeup of the protein can drastically alter its functions. Different changes to the wild type (WT) amino acid chain include post translational modifications (PTMs) and mutations. PTMs are additions of certain chemical groups to specific residues after the translation process. They change and expand the functions of mechanisms of the protein. A mutation can occur at the genetic level as a result of diseases, like cancer, and can change one of the residues to a different amino acid than it would be in the WT. Poly [ADP-ribose] polymerase 2 (PARP-2) is a protein that is present in the human body with the main function of mending DNA breaks. A PTM that adds a phosphate group to a serine can occur at residues 226, 232, and 353. Our group also uncovered a cancer-associated mutation on PARP-2 that changes what should be an aspartic acid in the WT to a glycine at position 235. To understand the effects of the phosphoserine PTMs and D235G mutation, four systems were simulated via molecular dynamics (MD) for 500 nanoseconds in triplicate, and different kinds of analysis were performed. The analysis included root mean square deviation, root mean square fluctuation, normal mode analysis, hydrogen bond analysis, matrix correlation analysis, difference correlation analysis, and hydrogen bond analysis. The results showed the impacts the modifications and mutation had to the movement and structure of the protein.