环聚糖作为淋病奈瑟菌PorB孔蛋白抗菌剂的计算模型：对接、免疫和分子动力学模拟的整合。

IF 3.8 3区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Frontiers in Chemistry Pub Date : 2024-11-25 eCollection Date: 2024-01-01 DOI:10.3389/fchem.2024.1493165

Muzamal Hussain, Nazia Kanwal, Alishba Jahangir, Nouman Ali, Nimra Hanif, Obaid Ullah

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引用次数: 0

摘要

背景：淋病奈瑟菌是导致淋病的细菌，淋病是全球最常见的性传播感染（STIs）之一。世界卫生组织（世卫组织）估计，2020年将有8240万新发淋病奈瑟菌感染病例。目前的治疗依赖于抗生素，但耐多药菌株的出现对公共卫生构成了重大威胁。本研究旨在利用计算模型建立环聚糖作为抗菌药物，靶向淋病奈瑟菌PorB Porin蛋白，抑制其致病性。方法：从蛋白质数据库（PDB ID: 4AUI）中检索PorB Porin蛋白，使用Discovery Visual Studio进行清洗和可视化。利用ProtParam对其理化性质进行了预测。从CyBase数据库中获得环潮汐，并通过Swiss Model生成3D模型并进行优化，用于对接研究。HDOCK用于分子对接。使用ToxinPred和AlgPred进行毒性和过敏原预测。使用Protein-Sol创建了肽的热图。利用Schrödinger LLC的Desmond软件进行100,000皮秒的分子动力学（MD）模拟，同时利用MMGBSA分析结合能。免疫反应模拟采用C-ImmSim 10.1软件，水中肽模拟采用WebGro软件。结果：该蛋白的肉汁值为-0.539，为中等亲水性，等电点为9.14，为基本性质。Globa D的对接评分最高（-270.04 kcal/mol），被认为是无毒和无过敏性的。MD模拟显示，MMGBSA具有稳定的蛋白质配体相互作用，其结合能较低，为-36.737 kcal/mol。免疫模拟表明Globa D具有有效的免疫反应，肽模拟表明Globa D在水中的稳定性，使其成为药物应用的潜在候选者。结论：Globa D通过抑制PorB Porin蛋白链a，成为抗淋病奈瑟菌的最佳候选药物，建议进一步的体内外研究来验证这些发现并探索临床应用。

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Computational modeling of cyclotides as antimicrobial agents against Neisseria gonorrhoeae PorB porin protein: integration of docking, immune, and molecular dynamics simulations.

Background: Neisseria gonorrhoeae is the bacterium responsible for gonorrhoea, one of the most common sexually transmitted infections (STIs) globally. In 2020, the World Health Organization (WHO) estimated 82.4 million new cases of Neisseria gonorrhoeae infections. Current treatments rely on antibiotics, but the emergence of multi drug resistance (MDR) strains poses a significant threat to public health. This research aims to use computational modeling of cyclotides as antimicrobial agents targeting the Neisseria gonorrhoeae PorB Porin protein to inhibit its pathogenicity.

Methodology: The PorB Porin protein was retrieved from the Protein Data Bank (PDB ID: 4AUI), cleaned, and visualized using Discovery Visual Studio. Physicochemical properties were predicted using ProtParam. Cyclotides were obtained from the CyBase database, with 3D models generated and refined via the Swiss Model for docking studies. HDOCK was used for molecular docking. Toxicity and allergenicity predictions were performed with ToxinPred and AlgPred. A heatmap of the peptide was created using Protein-Sol. Molecular dynamics (MD) simulations were conducted for 100,000 picoseconds using Desmond from Schrödinger LLC, while binding energy was analyzed using MMGBSA. Immune response simulations were done with C-ImmSim 10.1, and peptide simulation in water was performed via WebGro.

Results: The protein's GRAVY value is -0.539, indicating moderate hydrophilicity, and its isoelectric point is 9.14, suggesting a fundamental nature. Globa D had the highest docking score (-270.04 kcal/mol) and was deemed non-toxic and non-allergenic. MD simulations showed stable protein-ligand interactions, and MMGBSA revealed a low binding energy of -36.737 kcal/mol. Immune simulations indicated an effective immune response and peptide simulations demonstrated Globa D's stability in water, making it a potential candidate for pharmaceutical applications.

Conclusion: Globa D proved the best drug candidate against Neisseria gonorrhoeae by inhibiting PorB Porin protein chain A. Further in vitro and in vivo studies are recommended to validate these findings and explore clinical applications.

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来源期刊

Frontiers in Chemistry Chemistry-General Chemistry

CiteScore

8.50

自引率

3.60%

发文量

1540

审稿时长

12 weeks

期刊介绍： Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide. Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”. All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.