基于多生物学途径虚拟筛选人参皂苷Rg3治疗黑色素瘤的蛋白靶点  

Virtual Screening of Ginsenoside Rg3 in the Treatment of Melanoma Protein Targets Based on Multiple Biological Pathways

作　　者：陈靖峰 张诗琪 黄雨杭 唐乾[1] 王立皓 曹洪玉[1] 郑学仿[1] CHEN Jingfeng;ZHANG Shiqi;HUANG Yuhang;TANG Qian;WANG Lihao;CAO Hongyu;ZHENG Xuefang(Dalian University,Dalian,Liaoning,China,116622)

机构地区：[1]大连大学,辽宁大连116622

出　　处：《河南中医》2025年第2期263-271,共9页Henan Traditional Chinese Medicine

基　　金：国家自然科学基金项目(21601025,21571025,21601024);辽宁省教育厅基本科研项目(LJKQZ2021168);大连大学平台科研项目(202101ZD01);大连大学学科交叉项目(DLUXK-2023-YB-007)。

摘　　要：目的:采用多种生物信息学方法探讨人参皂苷Rg3治疗黑色素瘤的作用机制。方法:利用Genecards、在线人类孟德尔遗传数据库(Online Mendelian Inheritance in Man, OMIM)和治疗靶标数据库(Therapeutic Target Database, TTD)筛选黑色素瘤相关靶点。将靶点导入String数据库构建蛋白质互作(protein-protein interaction, PPI)网络,采用R语言igraph包拓扑分析后采用Cytoscape进行网络可视化。采用Discovery studio 2022(DS)分析靶蛋白的结合位点后进行Autodock Vina刚性和LibDock半柔性分子对接筛选人参皂苷Rg3治疗黑色素瘤的关键靶点。使用R语言对筛选出的关键靶点进行基因本体(Gene Ontology, GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)信号通路富集分析。采用分子动力学模拟方法探讨靶点蛋白-人参皂苷Rg3相互作用机制。结果:基于GeneCards、OMIM及TTD数据库筛选确定了341个疾病靶点。PPI网络拓扑分析鉴定出115个核心靶点。通过刚性和半柔性分子对接筛选出DNA甲基转移酶3A(DNA methyltransferases 3A,DNMT3A)、趋化因子CC亚家族受体2(CC subfamily receptor 2,CCR2)和趋化因子CXC亚家族受体4(CXC subfamily receptor 4,CXCR4)等19个关键靶蛋白与Rg3具有良好的结合亲和力。KEGG和GO富集分析表明CCR2、CXCR4、DNMT3A等蛋白参与机体的多种生物学功能和途径。分子动力学模拟分析证实了CCR2-Rg3、DNMT3A-Rg3与CXCR4-Rg3的稳定性。结论:DNMT3A、CCR2等为黑色素瘤治疗中人参皂苷Rg3的关键高选择性和高稳定性靶蛋白,人参皂苷Rg3可通过抗感染、调节免疫、影响细胞衰老等发挥抗黑色素瘤的作用,为进一步研究人参皂苷Rg3抗黑色素瘤的应用提供理论支持。Objective:To explore the mechanism of action of ginsenoside Rg3 in the treatment of melanoma by using multiple bioinformatics methods.Methods:Melanoma-related targets were screened using Genecards,the Online Mendelian Inheritance in Man(OMIM)database,and the Therapeutic Target Database(TTD).The targets were imported into the String database to construct a protein-protein interaction(PPI)network.After topological analysis using the igraph package in R language,the network was visualized with Cytoscape.After analyzing the binding sites of the target proteins,rigid docking with Autodock Vina and flexible docking with LibDock were used to screen the key targets of Rg3 in the treatment of melanoma.The key targets screened were subjected to Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis using R language.Molecular dynamics simulation was used to explore the interaction mechanism between the target proteins and ginsenoside Rg3.Results:Based on the GeneCards,OMIM and TTD databases,341 disease targets were screened and determined.A total of 115 core nodes were identified in the PPI network.Through rigid and semi-flexible molecular docking,19 key target proteins such as DNA methyltransferase 3A(DNMT3A),chemokine receptor 2(CCR2),and chemokine receptor 4(CXCR4)were screened out,which had good binding affinity with Rg3.KEGG and GO enrichment analysis indicated that CCR2,CXCR4,MAPK3 and other proteins were involved in multiple biological functions and pathways of the body.Molecular dynamics simulation analysis confirmed the stability of CCR2-Rg3,DNMT3A-Rg3 and CXCR4-Rg3.Conclusion:DNMT3A,CCR2 and other proteins are the key high-selectivity and high-certainty target proteins of Rg3 in melanoma.Ginsenoside Rg3 can exert anti-melanoma effects through anti-infection,immune regulation,and influencing cell senescence,providing theoretical support for further research on the application of ginsenoside Rg3 in anti-melanoma.

关 键 词：人参皂苷RG3 黑色素瘤 网络药理学 分子对接 分子动力学模拟 

分 类 号：R285.5[医药卫生—中药学]