基于药效团模型的DNA错配修复化合物筛选  

Screening of DNA Mismatch Repair Compounds Based on Pharmacophore Model

作　　者：王菲 刘飞远[2] 王毅 梁佳龙[2,3] 孙智勇 Wang Fei;Liu Feiyuan;Wang Yi;Liang Jialong;Sun Zhiyong(Shaanxi Institute for Food and Drug Control,Xi'an 710065,China;No.946 Hospital of People's Lieration Army Ground Force;School of Pharmacy,Air Force Medital University)

机构地区：[1]陕西省食品药品监督检验研究院,西安710065 [2]中国人民解放军陆军第946医院 [3]空军军医大学药学院

出　　处：《中国药师》2021年第6期1018-1025,共8页China Pharmacist

基　　金：军队后勤科研项目(编号:CLJ20J027)。

摘　　要：目的:找到一种具有DNA错配修复功能的化合物。方法:通过构建大肠埃希菌MutS蛋白受体与内源性配体之间的药效团模型,构建并筛选化合物数据库,使用分子对接和分子动力学模拟的方法,确认具有潜在DNA错配修复功能的先导化合物,并对其与受体蛋白之间的结合作用模式进行分析。结果:筛选得到了化合物52,分子动力学模拟显示该化合物与MutS蛋白之间能够形成稳定的相互作用关系。结论:化合物52可能是潜在的DNA错配修复先导化合物,该研究为下一步的活性实验奠定了理论基础。Objective:To find a compound with DNA mismatch repair function.Methods:By constructing a pharmacophore model between E.coli MutS protein receptor and endogenous ligand,the compound database was set up and screened.The lead compound with potential DNA mismatch repair function was confirmed by molecular docking and molecular dynamics simulation method,and the mode of binding between the compound and the receptor protein was analyzed.Results:Compound 52 was screened out and molecular dynamics simulations showed that the compound could form a stable interaction relationship with MutS protein.Conclusion:Compound 52 may be a potential lead compound for DNA mismatch repair.This study lays a theoretical foundation for the next activity experiment.

关 键 词：药效团模型 虚拟筛选 DNA错配修复 分子模拟 分子动力学模拟 

分 类 号：R914.2[医药卫生—药物化学]