{"title":"<i>In silico</i> Validation of <i>Pseudomonas aeruginosa</i> Exotoxin A Domain I Interaction with the Novel Human scFv Antibody.","authors":"Zahra Shadman, Samaneh Ghasemali, Safar Farajnia, Mojtaba Mortazavi, Atefeh Biabangard, Saeed Khalili, Leila Rahbarnia","doi":"10.2174/1871526523666230329104537","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pseudomonas (P.) aeruginosa is one of the leading causes of nosocomial infections. The pathogenicity of P. aeruginosa is related to its inherent antimicrobial resistance and the diverse virulence factors of this bacterium. Owing to the specific role of exotoxin A in P. aeruginosa pathogenesis, it is known as a promising therapeutic candidate to develop antibodies as an alternative to antibiotics.</p><p><strong>Objective: </strong>The present study aimed to validate the interaction between a single-chain fragment variable (scFv) antibody identified from an scFv phage library against domain I exotoxin A by bioinformatic tools.</p><p><strong>Methods: </strong>For this, several bioinformatics tools, including Ligplot, Swiss PDB viewer (SPDBV), PyMOL, I-TASSER, Gromacs, and ClusPro servers were used to evaluate the interaction of scFv antibody with P. aeruginosa exotoxin A. The I-TASSER server was utilized to predict the function and structure of proteins. The interaction of two proteins was analyzed using ClusPro tools. The best docking results were further analyzed with Ligplot, Swiss PDB viewer, and PyMOL. Consequently, molecular dynamics simulation was utilized to predict the stability of the secondary structure of the antibody and the binding energy of the scFv antibody to the domain I of exotoxin A.</p><p><strong>Results: </strong>As a result, we demonstrated that data from computational biology could provide proteinprotein interaction information between scFv antibody/domain I exotoxin A and offers new insights into antibody development and therapeutic expansion.</p><p><strong>Conclusion: </strong>In summary, a recombinant human scFv capable of neutralizing P. aeruginosa exotoxin A is recommended as a promising treatment for infections caused by P. aeruginosa.</p>","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":"23 5","pages":"e290323215113"},"PeriodicalIF":0.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Infectious disorders drug targets","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1871526523666230329104537","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Pseudomonas (P.) aeruginosa is one of the leading causes of nosocomial infections. The pathogenicity of P. aeruginosa is related to its inherent antimicrobial resistance and the diverse virulence factors of this bacterium. Owing to the specific role of exotoxin A in P. aeruginosa pathogenesis, it is known as a promising therapeutic candidate to develop antibodies as an alternative to antibiotics.
Objective: The present study aimed to validate the interaction between a single-chain fragment variable (scFv) antibody identified from an scFv phage library against domain I exotoxin A by bioinformatic tools.
Methods: For this, several bioinformatics tools, including Ligplot, Swiss PDB viewer (SPDBV), PyMOL, I-TASSER, Gromacs, and ClusPro servers were used to evaluate the interaction of scFv antibody with P. aeruginosa exotoxin A. The I-TASSER server was utilized to predict the function and structure of proteins. The interaction of two proteins was analyzed using ClusPro tools. The best docking results were further analyzed with Ligplot, Swiss PDB viewer, and PyMOL. Consequently, molecular dynamics simulation was utilized to predict the stability of the secondary structure of the antibody and the binding energy of the scFv antibody to the domain I of exotoxin A.
Results: As a result, we demonstrated that data from computational biology could provide proteinprotein interaction information between scFv antibody/domain I exotoxin A and offers new insights into antibody development and therapeutic expansion.
Conclusion: In summary, a recombinant human scFv capable of neutralizing P. aeruginosa exotoxin A is recommended as a promising treatment for infections caused by P. aeruginosa.
铜绿假单胞菌 Exotoxin A Domain I 与新型人类 scFv 抗体相互作用的硅学验证。
背景：铜绿假单胞菌（P. aeruginosa）是造成医院内感染的主要原因之一。铜绿假单胞菌的致病性与其固有的抗菌药耐药性和多种致病因子有关。由于外毒素 A 在铜绿假单胞菌致病过程中的特殊作用，它被认为是一种很有希望的治疗候选物质，可用于开发抗体以替代抗生素：本研究旨在通过生物信息学工具验证从 scFv 噬菌体文库中发现的单链片段可变（scFv）抗体与结构域 I 外毒素 A 之间的相互作用：为此，我们使用了多种生物信息学工具，包括 Ligplot、Swiss PDB viewer (SPDBV)、PyMOL、I-TASSER、Gromacs 和 ClusPro 服务器来评估 scFv 抗体与铜绿假单胞菌外毒素 A 的相互作用。使用 ClusPro 工具分析了两种蛋白质的相互作用。利用 Ligplot、Swiss PDB viewer 和 PyMOL 进一步分析了最佳对接结果。随后，利用分子动力学模拟预测了抗体二级结构的稳定性以及 scFv 抗体与外毒素 A 结构域 I 的结合能：结果：我们证明了计算生物学数据可以提供 scFv 抗体/外毒素 A 结构域 I 之间的蛋白质相互作用信息，并为抗体开发和治疗扩展提供了新的见解：总之，能够中和铜绿假单胞菌外毒素 A 的重组人 scFv 是一种治疗铜绿假单胞菌感染的有效方法。
期刊介绍：
Infectious Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in infectious disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in infectious disorders. As the discovery, identification, characterization and validation of novel human drug targets for anti-infective drug discovery continues to grow, this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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