花青素主要成分与HER-2激酶区的分子对接

Molecular docking of anthocyanins constituents and HER-2 kinase domain

摘要:

用分子对接方法预测天然植物化学物质与受体蛋白的相互作用位点并探究作用机制。利用MVD (Molecular Virtual Docker 5.5) 软件，以HER-2激酶区为受体模板建立活性位点，与12种花青素成分进行分子对接。结果表明12种化合物均能在同一活性腔中与HER-2激酶区对接 (MolDock Score: 苷元<–105 kJ/mol, 单葡糖苷<–130 kJ/mol)，主要作用力是疏水作用和氢键；该活性腔也是ATP与HER-2激酶区的结合 (MolDock Score= –161 kJ/mol) 位点，花青素的结合可能会干扰ATP与HER-2之间氢键的形成。提示花青素可能以竞争性结合方式阻碍ATP与HER-2的结合，抑制HER-2磷酸化激活及下游信号通路的激活，从而发挥抑癌活性。

Abstract:

Anthocyanins are a ubiquitous group of water-soluble plant pigments of the flavonoid family, with anticancer property through HER-2 signaling pathway. Nowadays, molecular docking plays an important role in exposing the active sites and obtaining the bioactive conformation involving protein-ligand interactions. According to the crystal structure of HER-2 kinase domain and 12 main antitumor compounds of anthocyanins as well as ATP, a molecular docking study was performed by MVD program. All 12 compounds could bind to the same cavity of HER-2 kinase domain by high affinity (MolDock Score< -105 kJ/mol for anthocyanidins, < -130 kJ/mol for anthocyanidins-glc), where hydrophobic force and hydrogen bond played key roles. Additionally, this cavity overlapped with ATP binding (MolDock Score= -161 kJ/mol) domain; the binding of anthocyanins presumably interfered the H bond formation between ATP and HER-2. These results indicate that anthocyanins may competitively bind to ATP binding site in HER-2 kinase domain by suppressing HER-2 activation and downstream signaling cascade. This may provide useful theoretical instruction for the molecular mechanism of HER-2 kinase activity inhibition by anthocyanins in cancer prevention and treatment.