芴酮衍生物与端粒G-四链体DNA的分子对接研究

Molecular docking research of fluorenone derivatives with telomeric G-quadruplex DNA

目的采用计算机分子对接技术,研究芴酮衍生物与端粒G-四链体DNA的相互作用,为建立合理的化合物虚拟筛选模型提供依据。方法使用SYBYL-X 2.0的分子对接模块,以2种结合了平面刚性骨架小分子的G-四链体DNA晶体结构为目标受体,在对接模型可靠性验证的基础上,选取经结构优化改造后的芴酮衍生物小分子为配体,以总评分为评价标准进行分子对接,研究小分子配体与G-四链体DNA的相互作用方式。结果通过对比实验活性数据,分子对接模型的总评分能较好地反映化合物的细胞毒性强弱,并给出了多种分子间的相互作用模式。结论通过分子模拟研究建立了比较可靠的对接模型,可在后续工作中指导化合物结构设计,寻找高活性抗肿瘤化合物。

Objective To investigate the interaction between fluorenone derivatives and telomeric G-quadruplex DNA by mo lecular docking technology,so as to provide a groundwork for the creation of a rational virtual screening model.Methods Using the docking module of SYBYL-X 2.0 software,the telomeric G-quadruplex DNA receptor model was established on the basis of two crystal structures of the telomeric G-quadruplex DNA-small molecule complexes,and the reliability of docking with the receptor model was verified before the docking research.Then,using the docking model,the interaction between the telomeric G-quadruplex DNA and the optimized structure fluorenone derivatives was investigated,with the total score as an estimating index.Results Compared with the experimental data,total score in the docking gave a good prediction of cytotoxic activities of compounds,and several different modes of molecular interactions were suggested by the docking research.Conclusion A reliable docking model has been established for the research on the small molecule ligands that interacts with the telomeric G-quadruplex DNA,which might be used to search for new ligands and guide the rational ligand compound design.