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p53-MDM2相互作用的抑制已经成为治疗癌症的新方法.本文将分子动力学模拟和MM-PBSA(molecular mechanics/passion-Boltzman surface area)方法结合起来研究MDM2-p53相互作用机制。结果证明范德华相互作用驱动了MDM2与p53的结合.基于残基-残基相互作用的计算不仅证明p53的三个残基Phe19′,Trp23′和Leu26′与MDM2有较强的相互作用,而且还发现另外两个残基Leu22′和Pro27′也与MDM2有较强的相互作用,这为抗癌药物的设计提供了新靶标.同时也证明CH-CH,CH-π和π-π相互作用驱动了p53在MDM2疏水性裂缝中的结合.
Inhibition of p53-MDM2 interaction has become a new approach to the treatment of cancer.This paper combines molecular dynamics simulations with the method of molecular mechanics / passion-Boltzman surface area (MM-PBSA) to study the mechanism of MDM2-p53 interaction. The results demonstrate that van der Waals interactions drive the binding of MDM2 to p53.The calculation based on the residue-residue interaction not only demonstrates that Phe19 ’, Trp23’ and Leu26 ’, the three residues of p53, have a strong interaction with MDM2 but also The other two residues, Leu22 ’and Pro27’, also showed strong interaction with MDM2, which provided a new target for the design of anticancer drugs. At the same time, it was also proved that CH-CH, CH-π and π-π interactions were driven P53 binding in MDM2 hydrophobic fissures.