表皮生长因子受体酪氨酸激酶结构域与其抑制剂染料木素的模拟对接

Molecular Docking of Epidermal Growth Factor Receptor Tyramine Kinase Domain and Its Inhibitor Genistein

摘要:

染料木素是表皮生长因子受体酪氨酸激酶结构域(EGFR-TK)高度特异的非竞争性抑制剂。本研究采用AutoDock3.05分子对接软件包对EGFR-TK与染料木素进行了模拟对接研究, 探究了二者的相互作用机制, 为染料木素的抗肿瘤机制提供理论依据。对接结果表明, 染料木素结合在EGFR-TK的活性腔中, 与EGFR-TK发生了强烈的相互作用, 结合自由能△G为-31.2 kJ/mol; 染料木素通过干扰TK催化活性结构中Lys721/Glu738离子对的形成而抑制了EGFR-TK的活性, 属于非竞争性结合和抑制作用; 在结合中, 疏水力和氢键发挥了重要作用。

Abstract:

Genistein is a high specific and noncompetitive inhibitor of epidermal growth factor receptor tyramine kinase domain (EGFR-TK). In the paper, a molecular docking between genistein and EGFR-TK was studied to explore the mechanism of their interaction and antitumor mechanism of genistein by Autodock 3.05 program. The results indicated that genistein located in the active cavity of EGFR-TK by high affinity (△G=?31.2 kJ/mol), and genistein inhibited EGFR-TK by interfering with forming of Lys721/Glu738 ion pair. The inhibition belonged to noncompetitive interaction, in which hydrophobic force and hydrogen bond played key roles.