磷脂酰肌醇3-激酶与其抑制剂芹菜素的分子对接

Molecular Docking of Phosphatidylinositol 3-Kinase and Its Inhibitor Apigenin

采用AutoDock3.05分子对接软件包,以磷脂酰肌醇3-激酶(PI3K)的晶体结构和芹菜素的空间结构为基础,对PI3K和芹菜素的相互作用机制进行了分子对接研究,为芹菜素的抗肿瘤机制提供理论依据.芹菜素是PI3K的有效抑制剂,分子对接结果表明,芹菜素与PI3K发生了强烈的结合作用,结合自由能达到-33.1 kJ.mol-1;结合位点位于该酶底物ATP的结合位点上,与底物形成竞争性结合,从而导致PI3K的酶活性受到抑制;在结合中,疏水力、氢键和静电作用力对芹菜素和PI3K复合物的形成与稳定发挥了重要作用.

According to crystal structure of Phosphatidylinositol 3-kinase （PI3K） and 3-D structure of apigenin, a molecular docking study on the mechanism of interaction between PI3K and apigenin was performed to provide some theoretical foundation for antitumor mechanism of apigenin by Autodock 3.05 program. Apigenin is a potent inhibitor on PI3K. The results from molecular docking indicated that apigenin could bind to PI3K by high affinity with -33. 1 kJ.mol-1 of AG; Apigenin located to the binding site of the substrate ATP in PI3K, competitively binded in the enzyme and accordingly to inhibit its activity. Hydrophobic, hydrogen bond and electrostatic forces played key roles in formation and stability of PI3K and apigenin complex.