冠状病毒的结构预测s2m接吻复合体和扩展双重复合体
Adam H Kensinger1, Joseph A Makowski1, Mihaela Rita Mihailescu1
1Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282, United States.
ACS physical chemistry Au
|July 29, 2025
概括
这项研究验证了用于预测RNA接吻复合体 (KC) 和扩展双重体 (ED) 结构的计算管道. 该方法准确地模拟了SARS-CoV-2RNA二极体,有助于抗病毒疗法设计.
科学领域:
- 结构生物学是结构生物学.
- 病毒学 病毒学
- 计算化学是一种计算化学.
背景情况:
- RNA接吻复合体 (KCs) 和扩展复合体 (EDs) 对病毒复制和治疗设计至关重要.
- 在SARS-CoV-2中,茎环II动机 (s2m) 模分体与宿主免疫反应有关,但缺乏3D结构数据.
- 了解s2m二聚体结构是解释稳定性差异和生物物理影响的关键.
研究的目的:
- 评估VFold3D/LA-IsRNA管道,用于预测RNA KC和ED的3D结构.
- 用实验性HIV-1 DIS KC和ED结构验证管道的准确性.
- 为抗病毒药物开发提供SARS-CoV-2s2m二次结构的原子洞察力.
主要方法:
- 通过对实验性HIV-1 DIS KC和ED结构进行盲目和参考预测,验证VFold3D/LA-IsRNA管道.
- 预测结构与实验数据的比较,包括NMR,冷EM和分子动力学 (MD) 模拟.
- 分析预测的SARS-CoV-2s2m二次结构和使用MD模拟的精细化.
主要成果:
- 在VFold3D/LA-IsRNA管道中,对HIV-1 DIS KCs和EDs (平均RMSD为3.28 Å) 实现了准确的预测.
- 预测的s2m二元结构显示了扭曲 (KCs) 或线性 (EDs) 形状,与PAGE迁移差异一致.
- SARS-CoV s2m KC 形成了堆叠的平行体基对三重体,而 SARS-CoV-2 和 Delta s2m 形成了正规基对,解释了二分体的不稳定性.
结论:
- VFold3D/LA-IsRNA管道可靠地生成3DRNA KC和ED结构.
- 预测的结构与实验数据保持一致,为病毒RNA二元稳定性提供了机械洞察力.
- 这项工作为设计针对病毒RNA结构的抗病毒疗法提供了基础.
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