基于分子对接研究黄酮及异黄酮类化合物与G-四链体DNA的相互作用

Study on the Interaction of Flavone and Isoflavone Derivatives with G-quadruplex DNA Based on Molecular Docking

目的:探讨端粒G-四链体DNA稳定剂黄酮及异黄酮类化合物的作用模式,进而确立比较可靠的化合物分子对接模型用于后续研究。方法:以两个具有与黄酮及异黄酮相似结构配体的G-四链体DNA晶体为受体,将文献中报道了活性的黄酮及异黄酮类化合物经过能量优化后作为配体,采用SYBYL-X 2.0的对接模块进行分子对接。通过对接总评分与活性数据对比来分析对接模型的合理性,同时研究化合物与G-四链体DNA的相互作用。结果:分子对接软件计算出的总评分与化合物活性数据比较匹配,预测的受体-配体间相互作用对化合物结构优化具有较好的参考意义。结论:通过分子模拟及结果分析建立了比较合理的对接模型,在下一步工作中可应用该模型进行虚拟筛选,指导化合物设计。

Objective: To explore the action mode of flavone and isoflavone derivatives as telomeric G-quadruplex DNA stabilizers,and to establish a more reliable compound molecular docking model for follow-up research. Methods: Taking two crystal structures of G-quadruplex DNA which contained similar ligands with flavone and isoflavone as receptors,the active flavonoids and isoflavone compounds which were reported in the literature used as ligands after energy optimization,and molecular docking was carried out with SYBYL-X 2.0 docking module. The rationality of the docking model was analyzed by comparing the total score of docking with the activity data,and the interaction between the compound and G-quadruplex DNA was also studied. Results: The total scores were in accordance with the cytotoxic activity of compounds,and the predicted interactions of receptor and ligand provided some suggestions for compounds structural optimization. Conclusion: Based on molecular modeling and results analysis,a rational model has been built for compounds design and virtual screening in further work.