Molecular dynamic simulation insights into the normal state and restoration of p53 function

• Published in: International journal of molecular sciences Vol. 13; no. 8; pp. 9709 - 9740
• Main Authors: Fu, Ting, Min, Hanyi, Xu, Yong, Chen, Jianzhong, Li, Guohui
• Format: Journal Article Book Review
• Language: English
• Published: Switzerland MDPI AG 01.08.2012; Molecular Diversity Preservation International (MDPI)
• Subjects: Animals; conformational change; Drug Design; Humans; MDM2; MDMX; Models, Molecular; molecular dynamic simulation; Molecular Dynamics Simulation; p53; Protein Conformation; protein-ligand interaction; protein-protein interaction; Review; Tumor Suppressor Protein p53 - chemistry; Tumor Suppressor Protein p53 - metabolism; MDMX; protein-ligand interaction; MDM2; protein-protein interaction; conformational change; molecular dynamic simulation; p53
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms13089709

As a tumor suppressor protein, p53 plays a crucial role in the cell cycle and in cancer prevention. Almost 50 percent of all human malignant tumors are closely related to a deletion or mutation in p53. The activity of p53 is inhibited by over-active celluar antagonists, especially by the over-expression of the negative regulators MDM2 and MDMX. Protein-protein interactions, or post-translational modifications of the C-terminal negative regulatory domain of p53, also regulate its tumor suppressor activity. Restoration of p53 function through peptide and small molecular inhibitors has become a promising strategy for novel anti-cancer drug design and development. Molecular dynamics simulations have been extensively applied to investigate the conformation changes of p53 induced by protein-protein interactions and protein-ligand interactions, including peptide and small molecular inhibitors. This review focuses on the latest MD simulation research, to provide an overview of the current understanding of interactions between p53 and its partners at an atomic level.