摘要
p53-MDM2相互作用已经成为治疗癌症药物设计的重要靶标。采用分子动力学模拟和MM-PBSA方法计算了肽类抑制剂PMI与MDM2的绝对结合自由能,通过基于残基的自由能分解方法计算了MDM2的各残基与PMI的相互作用。结果表明:CH-π、CH-CH和π-π相互作用驱动了PMI在MDM2疏水性裂缝中的结合;相关矩阵的计算表明PMI在一定程度上诱导了MDM2内部的相关运动。
The p53 - MDM2 interaction has been an important target of anti-cancer drug design. Molecular dynamics simulations coupled with molecular meehanics/Poisson Bohzmann surface area method （MM - PBSA ） are performed to calculate the absolute binding free energies of peptide inhibitor PMI. Residue-based free energy decomposition method is adopted to compute the interactions of separate residues of MDM2 with PMI. The results prove that the CH - π, CH - CH and π-π interactions drive the binding of the inhibitor PMI in the hydrophobic cleft of MDM2. The calculation of cross-correlation matrix shows that PMI results in the correlation motion in MDM2. The study will provide important dynamic information for anti-cancer drug designs.
出处
《山东建筑大学学报》
2013年第2期101-105,共5页
Journal of Shandong Jianzhu University
基金
国家自然科学基金项目(11274206)
山东省自然科学基金项目(ZR2011HM048)
山东建筑大学博士科研基金项目(XNBS1268)
