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

作　　者：周丁山[1] 张洁[2] 马福旺[1] ZHOU Ding-shan;ZHANG Jie;MA Fu-wang(PIVAS,Renmin Hospital of Wuhan University,Wuhan 430060,China;School of basic medical sciences,Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学人民医院静脉用药调配中心,武汉430060 [2]武汉大学基础医学院,武汉430071

出　　处：《国际药学研究杂志》2020年第2期132-135,142,共5页Journal of International Pharmaceutical Research

摘　　要：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.

关 键 词：抗肿瘤化合物 芴酮 G-四链体DNA 分子对接 

分 类 号：R914[医药卫生—药物化学] R73-34[医药卫生—药学]