Comparative Investigation of R213G Mutation in DNA-Binding Domain of P53 Protein via Molecular Dynamics Simulation

P53 is a tumor suppressor protein with numerous missense mutations identified in its gene. These mutations are observed in a vast number of cancers. R213G is one of them which has a role in metastatic lung cancers. In this research, R213G was studied in comparison with the wild type via molecular dynamics simulation.

For the three-dimensional structure of the wild-type P53 protein, chain A was used from crystallographic structure with PDB ID: 1TSR.  For R213G mutation, residue 213 of this structure was changed to glycine. Molecular dynamics simulation was repeated twice for 15 ns using Gromacs 5.1.2 software package, AMBER99SB force field, and TIP3P as water model. RMSD, RMSF, radius of gyration, and potential energy analyses were performed on resulted trajectories.

RMSF analysis showed that the R213G mutation changes the flexibility of 11 residues including R-248. These residues are not near the mutated position, but all of them are located on 220-250 fragment of this domain or are residues in the neighbor of this fragment. The radius of gyration and potential energy results confirmed a reduction in stability of this protein as a result of this mutation.

RMSF analysis of R213G mutation beside the changes in stability and radius indicated that this mutation could greatly affect the P53 interactions with other macromolecules.