作为炭疽杆菌核糖体蛋白 S8 抑制剂的柔性 RNA 合体:分子动力学模拟的启示

IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Pradeep Pant
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引用次数: 0

摘要

炭疽杆菌(Bacillus anthracis)是炭疽病的致病菌,对公共卫生和国家安全构成严重威胁,由于它能够形成具有持久生命力的弹性孢子,因此被认为是一种潜在的生物武器。即使是吸入或摄入微量的气溶胶孢子,也会导致大范围的疾病和死亡,这凸显了该细菌的强大杀伤力。炭疽杆菌未经治疗的死亡率高达 100%,是一种令人不安的生物恐怖主义候选菌。为了应对这一危急情况,我们采用了最先进的计算工具来构思和表征专为炭疽病定制的柔性 RNA 合剂疗法。通过移除每个核苷酸单元中的 C2'-C3' ,我们设计出了柔性 RNA 类似物的基础结构。利用炭疽杆菌核糖体蛋白 S8 与 RNA 合体复合物的晶体结构,我们通过广泛的全原子显式溶剂分子动力学模拟(400 ns,每个模拟 3 次),探索了修饰后的 RNA 合体-S8 蛋白复合物的结构、动态和能量方面,然后与对照系统进行了比较。我们的研究结果表明,与对照 RNA 合体相比,灵活的 RNA 合体通过更好的形状互补性和改进的 H 键网络增强了与 S8 蛋白的结合能力。这项研究为开发针对炭疽杆菌的 RNA 合道体疗法提供了宝贵的见解,为采取创新策略减轻这种可怕病原体的影响铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Flexible RNA aptamers as inhibitors of Bacillus anthracis ribosomal protein S8: Insights from molecular dynamics simulations

Flexible RNA aptamers as inhibitors of Bacillus anthracis ribosomal protein S8: Insights from molecular dynamics simulations

Bacillus anthracis, the causative agent of anthrax, poses a substantial threat to public health and national security, and is recognized as a potential bioweapon due to its capacity to form resilient spores with enduring viability. Inhalation or ingestion of even minute quantities of aerosolized spores can lead to widespread illness and fatalities, underscoring the formidable lethality of the bacterium. With an untreated mortality rate of 100%, Bacillus anthracis is a disconcerting candidate for bioterrorism. In response to this critical scenario, we employed state-of-the-art computational tools to conceive and characterize flexible RNA aptamer therapeutics tailored for anthrax. The foundational structure of the flexible RNA aptamers was designed by removing the C2’-C3’ in each nucleotide unit. Leveraging the crystal structure of Bacillus anthracis ribosomal protein S8 complexed with an RNA aptamer, we explored the structural, dynamic, and energetic aspects of the modified RNA aptamer – S8 protein complexes through extensive all-atom explicit-solvent molecular dynamics simulations (400 ns, 3 replicas each), followed by drawing comparisons to the control system. Our findings demonstrate the enhanced binding competencies of the flexible RNA aptamers to the S8 protein via better shape complementarity and improved H-bond network compared to the control RNA aptamer. This research offers valuable insights into the development of RNA aptamer therapeutics targeting Bacillus anthracis, paving the way for innovative strategies to mitigate the impact of this formidable pathogen.

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来源期刊
Biophysical chemistry
Biophysical chemistry 生物-生化与分子生物学
CiteScore
6.10
自引率
10.50%
发文量
121
审稿时长
20 days
期刊介绍: Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.
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