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相关概念视频

Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

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Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
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Protein Folding01:25

Protein Folding

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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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Protein Organization01:24

Protein Organization

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Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
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Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
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Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
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通过整合结构和进化约束的逆折叠模型推进蛋白质进化

Hongyuan Fei1, Yunjia Li2, Yijing Liu2

  • 1New Cornerstone Science Laboratory, Center for Genome Editing, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

Cell
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概括

基于人工智能的蛋白质工程约束 (AiCE) 提高了蛋白质进化的效率. 这种方法使用反向折叠模型和约束来设计高适应性突变,优于传统技术.

关键词:
美国基础编辑器优化进化合基因组编辑高适应性突变反向折叠蛋白质的演变基于结构的限制

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科学领域:

  • 生物技术
  • 计算生物学
  • 蛋白质工程

背景情况:

  • 传统的蛋白质工程方法面临着低成功率和高成本的挑战.
  • 目前的方法通常依赖于人类的专业知识和特定任务的模型,限制了可扩展性.

研究的目的:

  • 为高效的人工蛋白质进化引入基于人工智能的蛋白质工程 (AiCE) 约束.
  • 为了证明AiCE的多功能性和优越性比传统的蛋白质工程方法.

主要方法:

  • 使用通用的蛋白质逆折叠模型来采样序列.
  • 整合结构和进化约束来识别高适应性突变.
  • 将AiCE应用于各种蛋白质工程任务,包括去氨酶,核局部化序列,核酶和逆转录酶.

主要成果:

  • 在八个不同的蛋白质工程应用中取得了11%至88%的成功率.
  • 开发了新的基数编辑器:enABE8e (5-bp窗口),enSdd6-CBE (1.3倍更高的保真度) 和enDdd1-DdCBE (14.3倍更高的线粒体活性).
  • 证明了AiCE对不同大小的蛋白质的有效性,从数以万计的残留物.

结论:

  • AiCE是一种多功能且易于使用的突变设计方法.
  • AiCE 显著提高了蛋白质工程中的效率,可扩展性和通用性.
  • 开发的基础编辑器对精准医学和农业的应用有希望.