橙酮类DRAK2抑制剂的3D-QSAR及分子对接研究  

Study on 3D Quantitative Structure-Activity Relationship and Molecular Docking of Aurone DRAK2 Inhibitors

作　　者：李逸 王边琳 牛超[1] 侯雪玲[1] Li Yi;Wang Bianlin;Niu Chao;Hou Xueling(Key Laboratory of Chemistry of Plant Resources in Arid Regions,Xinjiang Technical Institute of Physics and Chemistry,Chinese Academyof Sciences,Urumqi,830011;University of Chinese Academy of Sciences,Beijing,100049)

机构地区：[1]中国科学院新疆理化技术研究所,中国科学院干旱区植物资源化学重点实验室,乌鲁木齐830011 [2]中国科学院大学,北京100049

出　　处：《化学通报》2022年第6期728-735,共8页Chemistry

基　　金：国家重点研发计划项目(2020YFE0205600)资助。

摘　　要：本文对橙酮类DRAK2抑制剂的化学结构与生物活性之间的关系进行研究。采用三维定量构效关系(3D-QSAR)中的比较分子力场分析(CoMFA)和比较分子相似性指数分析(CoMSIA)方法针对59个DRAK2抑制剂建立3D-QSAR模型,阐明了抑制剂化学结构与其生物活性之间的关系。所构建的CoMFA模型交叉验证系数(q^(2))为0.625,非交叉验证系数(r^(2))为0.811,标准偏差(S)为0.365,Fisher检验值(F)为59.971;所构建的CoMSIA模型q^(2)为0.62,r^(2)为0.846,S为0.333,F值为56.453。内部和外部验证参数表明,生成的3D-QSAR模型均具有良好的预测能力和显著的统计学可靠性。分子对接实验与等势图的一致性,进一步表明本次分子模拟是可靠的。本研究对发现新型的潜在的更高活性的橙酮类DRAK2抑制剂具有指导意义。In this article,the relationship between chemical structure and biological activity of DRAK2 inhibitors of the aurone was investigated.With methods of comparative molecular force field analysis(CoMFA)and comparative molecular similarity index analysis(CoMSIA),3 D-QSAR models of 59 DRAK2 inhibitors were established and the structure-activity relationship was clarified.The internal and external validation parameters indicated that the generated 3 D-QSAR models,including comparative molecular field analysis(CoMFA、q^(2)=0.625、r^(2)=0.811)and comparative molecular similarity indices analysis(CoMSIA、q^(2)=0.62、r^(2)=0.846),exhibit considerable prediction ability and significant statistical reliability.The consistency of the molecular docking experiments with the equipotential plots further demonstrates the reliability of the molecular simulations.The study contributes to the discovery of novel aurone analogues of DRAK2 inhibitors with potentially higher activity.

关 键 词：橙酮 DRAK2 3D-QSAR COMFA COMSIA 分子对接 

分 类 号：TQ460.1[化学工程—制药化工]