We have studied room-temperature structural and dynamic properties of the p53 DNA-binding domain in both DNA-bound and DNA-free states. A cumulative 55 ns of explicit solvent molecular dynamics simulations with the particle mesh Ewald treatment of electrostatics was performed. It was found that the mean structures in the production portions of the trajectories agree well with the crystal structure: backbone root-mean-square deviations are in the range of 1.6 and 2.0 angstrom. In both simulations, noticeable backbone deviations from the crystal structure are observed only in loop L6, due to the lack of crystal packing in the simulations. More deviations are observed in the DNA-free simulation, apparently due to the absence of DNA. Computed backbone B-factor is also in qualitative agreement with the crystal structure. Interestingly, little backbone structural change is observed between the mean simulated DNA-bound and DNA-free structures. A notable difference is observed only at the DNA-binding interface. The correlation between native contacts and inactivation mechanisms of tumor mutations is also discussed. In the H2 region, tumor mutations at sites D281, R282, E285, and E286 may weaken five key interactions that stabilize H2, indicating that their inactivation mechanisms may be related to the loss of local structure around H2, which in turn may reduce the overall stability to a measurable amount. In the L2 region, tumor mutations at sites Y163, K164, E171, V173, L194, R249, I251, and E271 are likely to be responsible for the loss of stability in the protein. In addition to apparent DNA contacts that are related to DNA binding, interactions R175/S183, S183/R196, and E198/N235 are highly occupied only in the DNA-bound form, indicating that they are more likely to be responsible for DNA binding.