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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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Multi-species Conserved Sequences02:51

Multi-species Conserved Sequences

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Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
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Protein-protein Interfaces02:04

Protein-protein Interfaces

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Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
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Conservation of Protein Domains02:26

Conservation of Protein Domains

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Protein and Protein Structure02:15

Protein and Protein Structure

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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.
A protein's shape is critical to its function. For example, an enzyme...
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Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

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相关实验视频

Updated: Jun 21, 2025

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

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通过多目标优化来设计蛋白序列的综合方法.

Lu Hong1, Tanja Kortemme1,2,3

  • 1Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, United States of America.

PLoS computational biology
|July 11, 2024
PubMed
概括
此摘要是机器生成的。

本研究介绍了计算蛋白质设计的进化多目标优化框架,增强序列恢复和减少偏差. 该方法集成了深度学习模型,以更有效地生成具有复杂规格的蛋白质.

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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
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Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
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相关实验视频

Last Updated: Jun 21, 2025

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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
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科学领域:

  • 计算生物学是一种计算生物学.
  • 蛋白质工程是一种蛋白质工程.
  • 生物信息学是一种生物信息学.

背景情况:

  • 深度学习的进步需要用于计算蛋白质设计的综合框架.
  • 当前的方法很难在生成性设计中连贯地结合各种模型和目标.

研究的目的:

  • 适应进化的多目标优化,在蛋白质设计中整合多种模型和目标.
  • 提高生成蛋白质设计过程的效率和准确性.

主要方法:

  • 使用非主导排序遗传算法II (NSGA-II) 作为核心优化框架.
  • 整合AlphaFold2和ProteinMPNN对客观空间定义的信心指标.
  • 开发了一个使用ESM-1v和ProteinMPNN进行序列重新设计的突变运算符.

主要成果:

  • 与直接的ProteinMPNN应用相比,RfaH本源序列恢复的偏差和变异显著减少.
  • 展示了该方法在折叠切换蛋白RfaH和更高维度问题 (PapD,calmodulin) 上的有效性.
  • 观察到的改进归因于信息突变运算子,并行代设计和帕雷托前方近似.

结论:

  • 进化多目标优化为复杂的蛋白质设计任务提供了强大的框架.
  • 拟议的方法增强了序列空间探索和设计候选者的多样性.
  • 这种可适应的方法对于具有复杂规格的生成性蛋白质设计具有广泛的相关性.