苯丙酸类eEF2K抑制剂的三维定量构效关系  

Three-Dimensional Quantitative Structure-Activity Relationship of Phenylpropionic Acid eEF2K Inhibitors

作　　者：黎玉梅 宋昱 温嘉童 曹洪玉[1] 于大永[1] 史丽颖[2] Li Yumei;Song Yu;Wen Jiatong;Cao Hongyu;Yu Dayong;Shi Liying(School of Life Sciences and Technology,Dalian University,Dalian 116622,China;Dalian University Institute of Materia Medica,Dalian 116622,China)

机构地区：[1]大连大学生命科学与技术学院,辽宁大连116622 [2]大连大学药物研究所,辽宁大连116622

出　　处：《南京师大学报（自然科学版）》2020年第4期135-142,共8页Journal of Nanjing Normal University(Natural Science Edition)

基　　金：辽宁省科学技术计划项目(2019ZD0564)。

摘　　要：设计开发新的真核延伸因子2激酶(eEF2K)抑制剂.首先通过分子对接技术分析了苯丙酸类化合物与eEF2K之间相互作用的关键氨基酸和结合方式,进而基于比较分子场法(CoMFA)和比较分子相似性指数分析法(CoMSIA)分别建立28个已知活性的eEF2K抑制剂的3D-QSAR模型,研究该类抑制剂化学结构与生物活性之间的三维定量构效关系.两个3D-QSAR模型活性数据pIC_(50)的预测值与真实值基本一致,表明两个模型均具有良好的预测能力和统计学意义.根据3D-QSAR模型所提供的立体场、静电场、疏水场、氢键供体场和氢键受体场所提供的信息提出了优化该类抑制剂结构的药物设计思路,可为eEF2K抑制剂的研究与开发提供理论指导.The study was to design and develop new Eukaryotic Extension Factor 2 Kinase(eEF2 K)inhibitors.Firstly,the key amino acids and binding modes of the interaction between phenylpropionic acid compounds and eEF2 K were analyzed by molecular docking technology.Then,based on comparative molecular field analysis(CoMFA)and comparative molecular similarity index analysis(CoMSIA),the 3 D-QSAR models of 28 known active eEF2 K inhibitors were established.The predicted values of pIC50 of the two 3 D-QSAR models were basically consistent with the true values,which showed that both models had good predictive ability and statistical significance.Based on the information provided by 3 D-QSAR model in three-dimensional field,electrostatic field,hydrophobic field,hydrogen-bonded donor field and hydrogen-bonded receptor field,the idea of drug design for optimizing the structure of these inhibitors is put forward,which can provide theoretical guidance for the research and development of eEF2 K inhibitors.

关 键 词：eEF2K 分子对接 抑制剂 作用方式 三维定量构效关系 

分 类 号：R914.2[医药卫生—药物化学]