几种天然产物与CASP3靶点的相互作用机制探索

Preliminary Study on Interaction Mechanism among Several Natural Products And CASP3 Target

目的:研究几种中药有效成分与CASP3靶点的相互作用,分析其作用机理及结构特征,为CASP3抑制剂的开发提供参考。方法:基于前期研究,本文选择几种天然产物的有效成分,采用分子对接和分子动力学方法模拟其与CASP3靶点之间的相互作用,通过作用力分析配体和靶点的作用机制。结果:筛选出的丹参酮IIA和野黄芩苷与CASP3靶点的结合能力较强,通过分子动力学方法分别获取了丹参酮IIA和野黄芩苷与CASP3结合的理论稳定结构。丹参酮IIA与CASP3中的Phe256、Ser205、Trp206等4个氨基酸残基具有疏水作用,形成1个氢键。野黄芩苷与CASP3靶点中的Ser249、Trp214、Trp206等9个氨基酸残基具有疏水作用,形成了7个稳定性不同的氢键,其中静电相互作用是其结合更为稳定的主要原因。结论:丹参酮IIA和野黄芩苷能与CASP3靶点形成较为稳定的结合结构,探索相似的结构有利于设计更有效的CASP3抑制剂。

This study was aimed to illustrate the interaction mechanism between Chinese herbal medicines and CASP3 target, and to analyze the structural characteristics of CASP3 inhibitors. Molecular docking, molecular dynamics and binding energy were employed to analyze the interactions and mechanism between CASP3 target and ligands which were screened from a series of nature products. The results showed that the binding forces of tanshinone IIA and scutellarin with CASP3 target were stronger than others. And the theoretical stable structures of tanshinone IIA and scutellarin combined with CASP3 target were obtained by molecular dynamics method. It also can be found that hydrophobic interaction was crucial for tanshinone IIA binding to amino acid residues of CASP3 such as Phe256, Ser205 and Trp206.Meanwhile, one hydrogen bond was formed between ligand and receptor. The main interactions between scutellarin and CASP3 target were found to arise from hydrophobic effect in ligand and nine amino acid residues of receptor（such as Ser249, Trp214, and Trp206）, four hydrogen bonds with different stabilities and electrostatic interaction. It was concluded that tanshinone IIA and scutellarin can form stable structures with CASP3 target. And their similar structures may be useful to screen effective CASP3 inhibitors.