黄酮苷类与表皮生长因子受体结合模式的理论研究

Theoretic studies on binding model between flavonoid glycosides and epidermal growth factor receptor

目的利用对接方法对黄酮苷类与表皮生长因子受体(epidermal growth factor receptor,EGFR)结合模式和能力进行理论研究。方法从RCSB Protein数据库检索EGFR晶体结构为受体,收集黄酮苷类配体,用Schrodinger 8.0软件对受体和配体进行对接计算,分析其作用模式和对接分数。结果EGFR和黄酮苷类配体能够较好对接,其作用模式大致分为Ⅰ、Ⅱ和Ⅲ3种,3位和2′位的取代对结合模式的影响较大,3、5、7、4′位取代的变化对结合能力影响较大。结论黄酮苷类化合物存在与EGFR较好的结合,其中可能有选择性和多靶标的EGFR抑制剂存在,其取代位置和方式可以影响结合模式和能力,对于研究黄酮苷类抗肿瘤药物具有参考价值。

Objective To study binding model and capacity between flavonoid glycosides and epidermal growth factor receptor （EGFR） with docking calculation. Methods Crystal structures of EGFR were downloaded from RCSB Protein Data Bank. Flavonoid glycosides were collected as the ligands. The software Schrodinger 8.0 was employed to dock the ligands into the receptors, and the binding models and docking scores were analyzed. Results Flavonoid glycosides and EGFR could bind well. The binding model could be classified into types Ⅰ , Ⅱ , and Ⅲ. Substitutions at position 3 and 2＇ mostly affect the binding model, and at position 3, 5, 7 and 4＇ mostly affect the binding capacity. Conclusion Among flavonoid glycosides, there might be selective EGFR inhibitors and multiple targeted PTKs inbibitors. The binding model and capacity can be affected by the substitution of different positions or groups. The results suggest that flavonoid glycosides be potential anti-tumor leads.