SARS-CoV-2:对关键的离子氨基酸突变的预测
Atlal M El-Assaad1, Tayssir Hamieh2
1Department of Electrical Engineering & Computer Science, University of Toledo (UT), Toledo OH 43606, USA; Department of Computer Science, Lebanese International University (LIU), Bekaa, Lebanon.
Computers in biology and medicine
|June 13, 2024
概括
这项研究确定了影响抗体结合的新的潜在SARS-CoV-2突变. 尖端蛋白S1中的特定突变可能会对病毒产生重大影响.
科学领域:
- 病毒学和免疫学 病毒学和免疫学
- 计算生物学 计算生物学
- 结构生物学 结构生物学
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 导致COVID-19,正在进行对变体和突变的研究.
- 病毒尖端蛋白 (S) 对宿主细胞的附着和融合至关重要,使其突变成为疫苗和治疗开发的关键焦点.
- 抗体CC12.1针对的是SARS-CoV-2尖端蛋白S1亚单元.
研究的目的:
- 研究SARS-CoV-2尖端蛋白S1中离子氨基酸突变对其与抗体CC12.1.1.结合的影响.
- 识别可能影响病毒结合和免疫逃避的潜在新突变.
主要方法:
- 使用蛋白质静电相似性分析 (AESOP) 框架进行具有约束力的自由能量计算.
- 采用了自适应式波松-博尔兹曼溶解器 (APBS) 来计算静电电位.
- 使用PDB2PQR软件来确定SARS-CoV-2:CC12.1复杂模型中的APBS计算的原子半径和电荷.
主要成果:
- 鉴定了K378A,R408A,K424A,R454A,R457A,K458A和K462A突变,作为强大的抑制剂,抗体CC12.1与S1蛋白结合.
- 鉴定了D405A,D420A和D427A突变,作为与S1蛋白结合的抗体CC12.1的温和抑制剂.
- 这些发现代表了首次对超出目前已知的变种的潜在危及生命的SARS-CoV-2突变进行形鉴定.
结论:
- 在SARS-CoV-2尖端蛋白S1中的特定离子氨基酸替代物显著改变了与抗体CC12.1.1.的结合亲和力.
- 鉴定的突变可能代表治疗策略的新目标,或有助于病毒免疫逃脱.
- 这种计算方法为病毒进化和抗体相互作用提供了宝贵的见解.
相关概念视频
Single Nucleotide Polymorphisms-SNPs
15.0K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.0K
Mutations
81.8K
Overview
81.8K
Viral Mutations
32.2K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.2K
From DNA to Protein
18.3K
The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
18.3K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K


