德尔塔SARS-CoV-2s2m结构,动力学和:G15U突变的后果
Joseph A Makowski1, Adam H Kensinger1, Caylee L Cunningham1
1Department of Chemistry and Biochemistry and Center for Computational Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282, United States.
ACS physical chemistry Au
|October 2, 2023
概括
德尔塔SARS-CoV-2变种的s2mRNA结构比原来的SARS-CoV-2更为线性和不那么稳定,这解释了同体化中的差异. 这项研究揭示了Delta s2m基因中的关键结构和热力学变化.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 与祖先的SARS-CoV-2相比,Delta SARS-CoV-2变种在茎循环II动机 (s2m) 中具有单个核酸突变 (G15U).
- 以前的同体化实验显示了SARS-CoV-2和三角形SARS-CoV-2s2m之间的意想不到的差异,需要对潜在的结构和热力学变化进行调查.
研究的目的:
- 调查SARS-CoV-2 s2m和Delta SARS-CoV-2 s2m之间的结构,动态和热力学差异.
- 为了合理化两个SARS-CoV-2变体之间的s2m同极化观察到的差异.
主要方法:
- 在报告的SARS-CoV-2s2m模型中诱导了G15U替代.
- 在283K和310K进行了3.5微秒的无偏分子动力学模拟.
- 分析了二级和三级结构,螺旋参数,动力学和.
主要成果:
- 德尔塔s2m采用了更线性的发针结构,缺乏在SARS-CoV-2s2m中观察到的特征性的L形曲,这是由于纠正了上茎缺陷.
- 与SARS-CoV-2s2m相比,Delta s2m平行体序列的波动增加导致了估计在310K时6.8kcal/mol的热处罚,与SARS-CoV-2s2m相比.
- 这些结构和的差异解释了在Delta s2m中减少的自发性同质化和形成更少的接吻二次体和扩展的双重体.
结论:
- 在Delta s2m中减少的L形状和增加的平行体热惩罚为观察到的体外电泳学同质化差异提供了机制性的解释.
- 这项研究为了解s2m结构和动态变异在病毒生命周期中的作用奠定了基础.
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