Based on Molecular Docking, Molecular Dynamics Simulation and MM/PB(GB)SA to Study Potential Inhibitors of PRRSV-Nsp4.

IF 3.2 4区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Proteins-Structure Function and Bioinformatics Pub Date : 2025-03-01 Epub Date: 2024-10-11 DOI:10.1002/prot.26754

Tianyu Shi, Wenzhou Chang, Xinyu Wei, Yiling Kong, Ying Wei

{"title":"Based on Molecular Docking, Molecular Dynamics Simulation and MM/PB(GB)SA to Study Potential Inhibitors of PRRSV-Nsp4.","authors":"Tianyu Shi, Wenzhou Chang, Xinyu Wei, Yiling Kong, Ying Wei","doi":"10.1002/prot.26754","DOIUrl":null,"url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome (PRRS) is one of the most serious infectious immunosuppressive diseases in the world. The nonstructural protein Nsp4 can be used as an ideal target for anti-PRRSV replication inhibitors. However, little is known about potential inhibitors that target Nsp4 to affect PRRSV replication. The purpose of this study was to screen potential natural inhibitors that affect PRRSV replication by inhibiting Nsp4. Five compounds with strong binding affinity to Nsp4 were selected by structure-based molecular docking method. The complexes of naringin dihydrochalcone (NDC), agathisflavone (AGT), and amentoflavone (AMF) with Nsp4 were stable throughout the molecular dynamics simulation. According to MM/PBSA analysis, the free energies of binding of NDC, AGT, and AMF to Nsp4 were less than-30 Kcal/mol. In conclusion, these three compounds are worthy of further investigation as novel inhibitors of PRRSV. This study provides a theoretical basis for the development of anti-PRRSV natural drugs.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"598-607"},"PeriodicalIF":3.2000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proteins-Structure Function and Bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/prot.26754","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/11 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is one of the most serious infectious immunosuppressive diseases in the world. The nonstructural protein Nsp4 can be used as an ideal target for anti-PRRSV replication inhibitors. However, little is known about potential inhibitors that target Nsp4 to affect PRRSV replication. The purpose of this study was to screen potential natural inhibitors that affect PRRSV replication by inhibiting Nsp4. Five compounds with strong binding affinity to Nsp4 were selected by structure-based molecular docking method. The complexes of naringin dihydrochalcone (NDC), agathisflavone (AGT), and amentoflavone (AMF) with Nsp4 were stable throughout the molecular dynamics simulation. According to MM/PBSA analysis, the free energies of binding of NDC, AGT, and AMF to Nsp4 were less than-30 Kcal/mol. In conclusion, these three compounds are worthy of further investigation as novel inhibitors of PRRSV. This study provides a theoretical basis for the development of anti-PRRSV natural drugs.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

基于分子对接、分子动力学模拟和 MM/PB(GB)SA 研究 PRRSV-Nsp4 的潜在抑制剂

猪繁殖与呼吸综合征（PRRS）是世界上最严重的传染性免疫抑制疾病之一。非结构蛋白 Nsp4 可作为抗 PRRSV 复制抑制剂的理想靶点。然而，人们对以 Nsp4 为靶点影响 PRRSV 复制的潜在抑制剂知之甚少。本研究旨在筛选通过抑制 Nsp4 来影响 PRRSV 复制的潜在天然抑制剂。通过基于结构的分子对接方法，筛选出五种与Nsp4结合亲和力强的化合物。在整个分子动力学模拟过程中，柚皮苷二氢查尔酮（NDC）、琼脂糖黄酮（AGT）和门冬酰胺黄酮（AMF）与Nsp4的复合物非常稳定。根据 MM/PBSA 分析，NDC、AGT 和 AMF 与 Nsp4 结合的自由能小于-30 Kcal/mol。总之，这三种化合物作为 PRRSV 的新型抑制剂值得进一步研究。这项研究为开发抗 PRRSV 天然药物提供了理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Proteins-Structure Function and Bioinformatics 生物-生化与分子生物学

CiteScore

5.90

自引率

3.40%

发文量

172

审稿时长

3 months

期刊介绍： PROTEINS : Structure, Function, and Bioinformatics publishes original reports of significant experimental and analytic research in all areas of protein research: structure, function, computation, genetics, and design. The journal encourages reports that present new experimental or computational approaches for interpreting and understanding data from biophysical chemistry, structural studies of proteins and macromolecular assemblies, alterations of protein structure and function engineered through techniques of molecular biology and genetics, functional analyses under physiologic conditions, as well as the interactions of proteins with receptors, nucleic acids, or other specific ligands or substrates. Research in protein and peptide biochemistry directed toward synthesizing or characterizing molecules that simulate aspects of the activity of proteins, or that act as inhibitors of protein function, is also within the scope of PROTEINS. In addition to full-length reports, short communications (usually not more than 4 printed pages) and prediction reports are welcome. Reviews are typically by invitation; authors are encouraged to submit proposed topics for consideration.