CAJ | 학술논문

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-x l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。
목적：자초소연생물인기량호적항종류활성흡인료흔다연구자적흥취。단시환몰유침대기여가능파표단백Bcl-x l적작용모식적연구，차문이기통과계산궤모의지도신화합물적설계화합성。방법채용분자대접화분자동역학모의적방법，연구료화합물Comp A여Bcl-xl지간적상호작용모식，병대상호작용진행료분석。결과 Bcl-xl활성위점구역적전하분포정황여자초소연생물지간적상호작용결정료화합물적활성，재고근 A 구、B구개선소분자적특성，가증가량자적상호작용화소분자활성。결론통과계산궤모의조도료자초소연생물결구우화적방향，가이용우지도화합물적합성화수식。
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 .