紫草素衍生物与Bcl-xl靶标的相互作用的分子模拟研究

Molecular simulation study on shikonin derivatives as potent Bcl-xl inhibitors

目的紫草素衍生物因其良好的抗肿瘤活性吸引了很多研究者的兴趣。但是还没有针对其与可能靶标蛋白Bcl-xl的作用模式的研究,此文以期通过计算机模拟指导新化合物的设计和合成。方法采用分子对接和分子动力学模拟的方法,研究了化合物Comp A与Bcl-xl之间的相互作用模式,并对相互作用进行了分析。结果 Bcl-xl活性位点区域的电荷分布情况与紫草素衍生物之间的相互作用决定了化合物的活性,在靠近A区、B区改善小分子的特性,可增加两者的相互作用和小分子活性。结论通过计算机模拟找到了紫草素衍生物结构优化的方向,可以用于指导化合物的合成和修饰。

Objective Shikonin and its derivatives have attracted considerable attention in view of their anti-tumor biological activi-ties .But there are no the studies of interaction between shikonin derivatives and Bcl-xl until now .In this paper ,we used the mo-lecular simulation to guide the design and synthesis of new compounds .Methods Molecular docking and dynamics simulations were carried out to explore the best binding mode and the interaction of Comp A and Bcl-xl .Results The activity of shikonin de-rivatives was influenced by charge distribution around the active site .The corresponding structural modification of small molecules near zone A and B could enhance their interaction and improve activity .Conclusion In this study ,molecular simulations were used to obtain insights into the structural requirements of inhibitors ,which could be helpful to direct the design of new shikonin deriva-tives as potent anti-tumor agents .