title: Molecular dynamic simulation insights into the normal state and restoration of p53 function.
abstract: 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.
authors.affiliation: Laboratory of Molecular Modeling and Design, State key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.|Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian 116024, China.|Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Fu
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
authors.forename: Hanyi
authors.initials: H
authors.lastname: Min
authors.affiliation: Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Mathematics and Physics, Shandong Jiaotong University, Jinan 250031, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Modeling and Design, State key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53