Structural Point Mutations of p53 Protein and Their Effects on the Zinc Coordination Complex
Taylor Quinn, Vassar College ’15 and Prof. Kelly M. Thayer
The p53 protein is an important transcription factor in the cell cycle. As such, mutations of this protein are found in at least 50% of all cancers, most of which are in the DNA-binding domain containing residues 102-292. This research is focusing on the molecular dynamics of p53 with point mutations that affect the structural stability of the protein, namely, R175H, R282W, G245S, and R249S. The system will be evaluated in reference to the Zn2+ cation that is tetrahedrally coordinated to Cys176, Cys238, Cys242, and His179. Changes in the stability of the coordination complex have been shown to have a greater effect on the stability of the overall protein, as it restricts the movement of the L2 and L3 loops. The mutations changing the structure of the protein ultimately have an effect on the stability of the zinc complex, which can be detrimental to DNA and protein binding activity. Previous research has shown that there are five different clusters of DNA sequences that the protein binds to, and all are being evaluated in reference to the p53 protein and its mutations. These systems and their changes are evaluated using molecular dynamic simulations with the AMBER12 suite, cpptraj, VMD and PyMOL. Results and analysis will be presented.