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应用ABEEM/MM分子力场结合ABEEMσπ/GB/SA方法,分别研究了内酯和羧酸盐形式喜树碱以及不含内酯结构的S39625与Top1-DNA复合物相互作用的结合自由能.从计算得到的结合自由能以及相互作用的结构分析上来看,羧酸盐形式的喜树碱与Top1cc结合的更稳定,不含内酯结构的S39625也表现出和喜树碱相类似的结合Top1cc的能力.由此看来,内酯结构并非是喜树碱捕获DNA拓扑异构酶的必要条件,羧酸盐形式的喜树碱由于带一个负电荷而具有更强的结合能力.研究从分子水平上揭示了喜树碱的结构对抗癌活性的影响,将有助于设计和发展该类抗癌药物的合成.
The ABEEM / MM molecular force field combined with the ABEEMσπ / GB / SA method was used to study the free energy of the interaction between the lactone and carboxylate camptothecins and the S39625 without the lactone structure and the Top1-DNA complex. Calculated Free Radical Bonding and Structural Analysis of Interactions A more stable, lactone-free, S39625 bound carboxylate form of camptothecin to Top1cc also exhibits similar camptothecin binding to Top1cc Capacity.Thus, the lactone structure is not a necessary condition for camptothecin to capture DNA topoisomerase, and the carboxylate form of camptothecin has a stronger binding ability due to a negative charge.Studies on the molecular level Reveal the camptothecin structure on anticancer activity will help design and development of such anti-cancer drug synthesis.