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相关概念视频

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ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
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Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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线性CDSfold:一种用于在编码序列设计中共同优化二级结构稳定性和密码子使用的工具.

Yu-Shen Liu1, Yan-Ru Ju1, Kai-Wei Chang1

  • 1Department of Computer Science, National Tsing Hua University, Hsinchu 30013, Taiwan.

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概括
此摘要是机器生成的。

线性CDSfold现在可以有效地生成帕雷托-最佳的mRNA编码序列 (CDS) 用于疫苗设计. 该工具优化了RNA二级结构稳定性和密码子的使用,为现有方法提供了更快的替代方案.

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科学领域:

  • 生物信息学是一种生物信息学.
  • 计算生物学 计算生物学
  • 合成生物学 合成生物学

背景情况:

  • 设计用于疫苗的mRNA编码序列 (CDS) 需要优化RNA二次结构稳定性 (最小自由能量,MFE) 和子使用 (子适应指数,CAI).
  • 现有的工具往往难以平衡这些相互竞争的目标,需要产生帕雷托最佳CDS的方法,其中没有一个目标可以在不恶化另一个目标的情况下得到改善.

研究的目的:

  • 增强LinearCDSfold工具,以自动和高效地生成帕雷托最佳的CDS.
  • 为在mRNA疫苗设计中共同优化MFE和CAI提供一个优质的替代方案.

主要方法:

  • 在LinearCDSfold框架内利用动态编程和光束搜索技术.
  • 扩展线性CDS折叠生成一组帕雷托最佳的CDS,同时考虑MFE和CAI.
  • 在九个不同的蛋白质序列上评估了性能.

主要成果:

  • 增强的LinearCDSfold可以高效地生成帕雷托最佳的CDS.
  • 在帕雷托最佳集生成方面,性能与现有工具DERNA相美.
  • 与DERNA相比,LinearCDSfold的运行时间明显更快.

结论:

  • 线性CDSfold是一种强大而高效的工具,用于为mRNA疫苗开发生成帕雷托最佳的CDS.
  • 增强版提供了显著的速度优势,加速了设计过程.
  • 这一进步有助于在合成生物学应用中协同优化RNA结构和密码子的使用.