基于计算机分子模拟技术从天然产物中筛选PPARγ激动剂  

Screening of PPARγ agonists from natural products based on computer molecular modeling

作　　者：刘治国 崔文强 魏叶 朱心瑶 杨雪[1] Liu Zhiguo;Cui Wenqiang;Wei Ye;Zhu Xinyao;Yang Xue(Suqian First People's Hospital Affiliated to Nanjing Medical University,First People's Hospital of Suqian City,Suqian 223800,China;Northeast Agricultural University,Harbin 150030,China;Xuzhou Medical University,Xuzhou 221004,China)

机构地区：[1]南京医科大学附属宿迁第一人民医院,宿迁市第一人民医院,宿迁223800 [2]东北农业大学,哈尔滨150030 [3]徐州医科大学,徐州221004

出　　处：《国际医药卫生导报》2022年第9期1204-1208,共5页International Medicine and Health Guidance News

基　　金：江苏省“六大人才高峰”项目(WSN-342);江苏省青年医学重点人才项目(QNRC2016480);宿迁市科技计划项目(S201720)。

摘　　要：目的采用分子对接技术从天然产物中筛选PPARγ激动剂。方法研究时间为2021年1月至9月。基于过氧化物酶体增殖物激活受体γ(PPARγ)的PDB晶型结构(PDBCode:6md4),构建虚拟靶标模型,以天然产物数据库中的1680个化合物为配体筛选对象,以6md4原配体分子为对照。首先采用SYBYL软件对天然小分子化合物进行虚拟筛选,随后对排名前20位的化合物进行高精度分子对接,最后再使用PyMol软件分析结合稳定的化合物。结果根据评分结果并结合冲突、极性和相似度,最终筛选出橙皮苷等20个小分子PPARγ激动剂,其中橙皮苷能够与PPARγSer289、His323、Tyr327等多个氨基酸形成氢键,结合良好。结论从天然产物中筛选出潜在的PPARγ激动剂,为发现新型抗糖尿病的先导化合物或膳食补充剂提供基础。Objective To screen PPARγagonists from natural products by molecular docking.Methods This study was from January to December 2021.Based on the crystal structure of peroxisome proliferator-activated receptor gamma(PPARγ)(PDB Code:6md4),a virtual target model was constructed.A total of 1680 compounds in the natural product database were used as the ligands for screening,and the 6md4 pro-ligands were used as control.Firstly,the SYBYL software was used for the virtual screening of natural small molecular compounds,followed by high-precision molecular docking of the top 20 compounds,and finally the PyMol software was used to analyze the stable binding compounds.Results According to the scoring results,crash,polar,20 small-molecule PPAR gamma agonists,such as hesperidin,and the like,were finally screened out.Among them,hesperidin could form hydrogen bonds with many amino acids,such as PPARγSer289,His323,Tyr327,and so on.Conclusion The potential PPARγagonists were screened from natural products so as to provide basis for the discovery of new anti-diabetic lead compounds or dietary supplements.

关 键 词：2型糖尿病 PPARΓ 计算机虚拟筛选 分子对接 

分 类 号：R965.1[医药卫生—药理学]