Introduction: P53, a tumor suppressor protein has as negative regulator, the MDM2 oncoprotein. Inhibition of p53–MDM2 interaction is a promising approach for activating p53, since this association is well characterized structurally and biologically. We study two complexes of MDM2 that were described by crystallographic data so far. The behavior of these two complexes in solution was not yet completely characterized, so in this work we compare them using Molecular Dynamics (MD) simulation. Objective: This study aims to analyze the interaction of MDM2 with the synthetic FMNYWEGL (PDB code 1t4f) and native p53 ETFSDLWKLPEN (PDB code 1ycr) peptides, focusing in structural variations, atomic details at intermolecular contact surface and H-bonds stability, under dynamic point of view. Methods: The systems were optimized by Steepest Descent and Conjugated Gradient methods using GROMACS package. After this, we carried out MD simulations in both systems: 0.5 ns with protein atom positions restrained, then more 0.5ns for equilibration of solvent and finally 10 ns of full MD for data acquisition in both systems. Results: The comparison of the crystallographic B Factor with the one obtained from the MD trajectories showed variation on the atoms movement at the beginning (residues 1 to 17) and end of MDM2 (residues 81 to 85) and at peptide regions (89 to 97). Calculations of the contact surface area demonstrated that Phe19, Trp23 and Leu26 are the most important hydrophobic residues on the interaction, as previous described by experimental data. Additionally, we observed that more than 50% of interaction surface area is based in hydrophobic amino acids. It was observed 25 direct and 14 water intermediated H-bonds between MDM2 and the p53 peptide and 13 direct and 5 intermediated in the other complex. Conclusion: The time prevalence of H-bonds was about 20% in both complexes. Based on our simulation results we specified the structural and dynamic way the synthetic peptide could act as a good competitor with native p53 for MDM2. So, with MD we could have a better understanding of these complexes. This information can assist the development of inhibiting drugs of oncogenic action of MDM2.