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Sajjad Haider1, Nadeem Ahmad1, Muhammad Shafiq1
1H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
像XBB.1.5和CH.1.1这样的新Omicron亚型显示出由于与人类ACE2受体的结合稳定性提高而增加的传播能力. 分子动力学模拟显示,这些变体比野生类型的Omicron更有效地结合.
科学领域:
- 病毒学和分子生物学
- 计算生物学和生物信息学
背景情况:
- 由SARS-CoV-2引起的COVID-19大流行,已经出现了包括Omicron在内的众多关注变种 (VOC).
- 奥米克朗变种,特别是像XBB.1.5和CH.1.1这样的亚变种,表现出增加的传播能力,部分原因是尖端蛋白的受体结合域 (RBD) 的突变.
- 尖端蛋白与人类血管酶转化酶2 (hACE2) 受体的相互作用对于病毒的进入和感染性至关重要.
研究的目的:
- 调查SARS-CoV-2 Omicron亚型XBB.1.5和CH.1.1与人类ACE2受体复合的分子动力学和结合稳定性.
- 使用计算方法,将这些亚变体的结合亲和力和结构稳定性与野生型Omicron变体进行比较.
主要方法:
- 在总计1.65μs的分子动力学 (MD) 模拟中使用,以分析尖端蛋白-hACE2复合体的结构稳定性.
- 评估结构稳定性使用参数,如根-平均-平方偏差 (RMSD),根-平均-平方波动 (RMSF) 和旋转半径 (Rg).
- 使用MM-GBSA (分子力学与一般化出生表面积) 方法确定结合的自由能量,以量化结合亲和力.
主要成果:
- 与野生型 (WT) Omicron相比,未结合的突变尖端蛋白框架 (SM和TM) 显示出更大的不稳定性.
- WT Omicron-hACE2复合体比SM-hACE2和TM-hACE2复合体不太稳定,这表明子变体的稳定性增加了.
- 在MM-GBSA的计算中,SM-hACE2和TM-hACE2复合物的结合自由能量值更高,这表明结合相互作用更稳定和有序.
结论:
- 欧米克朗亚型XBB.1.5和CH.1.1与HACE2受体的增强结合稳定性和有序相互作用有助于它们的传染性增加.
- 计算模拟提供了对新型SARS-CoV-2变异的进化优势背后的分子机制的宝贵见解.
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