p53-MDM2结合抑制剂药效团模型的构建

Pharmacophore Model Construction of p53-MDM2 Binding Inhibitors

采用Catalyst软件,选择5类共24个p53-MDM2结合抑制剂作为训练集,经计算机建模、构象优化。由Catalyst系统构建出药效团模型,并对药效团进行有效性分析,结合已知的p53-MDM2结合抑制剂的结构信息,筛选得到含有一个芳环中心、三个疏水中心和一个氢键受体的具有较好预测能力(Correl=0.941,Config= 17.530,Δcost=150.830)的药效团模型.

The pharmacophore model of p53-MDM2 binding inhibitors was established by the Catalyst software with the training set of 24 inhibitors containing 5 different kinds of structures. Based on the information of p53- MDM2 binding structure, a fitting pharmacophore model （Correl=0.941, Config=17.530, A cost=150.830） including one hydrogen-bonding acceptor, one aromatic ring center and three aliphatic hydrophobic cores was confirmed. The pharmacophore model could be used to screen new lead compound of p53-MDM2 binding inhibitor.