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相关概念视频

Assembly of Cytoskeletal Filaments01:18

Assembly of Cytoskeletal Filaments

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Cytoskeletal filaments are polymeric forms of smaller protein subunits. However, individual cytoskeletal filaments may easily disassemble or associate with other similar filaments to form rigid structures. Microfilaments, made of actin monomers, rely on actin-binding proteins to form bundles and create networks of individual actin filaments. Microtubules rely on microtubule-associated proteins (MAPs) to form sturdy cylindrical structures. However, the proteins involved in forming complex...
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Automated Robotic Liquid Handling Assembly of Modular DNA Devices
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使用自动差异化发现自组合的最佳运动路径.

Adip Jhaveri1, Spencer Loggia1, Yian Qian1

  • 1TC Jenkins Department of Biophysics, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218.

bioRxiv : the preprint server for biology
|September 11, 2023
PubMed
概括

这项研究使用深度学习来优化宏分子自我组装,找到有效的策略来避免动力陷并最大限度地提高产品产量. 不同的子单元设计和外部控制协议证明对高产量组装最有效.

科学领域:

  • 生物物理学的生物物理.
  • 系统生物学 系统生物学
  • 计算化学计算化学

背景情况:

  • 巨分子自我组装对于生物结构如核糖体和病毒囊体至关重要,但由于动力陷,其产量往往会减少.
  • 设计合成组装系统需要了解生物策略,以避免这些陷并实现高效的组装.

研究的目的:

  • 优化可逆自组合的物理模型,使用自动差异化来发现避免动力陷的策略.
  • 在速率常数参数空间中为3-7个子单元复合体识别多样化的解决方案.

主要方法:

  • 利用来自深度学习框架的自动区分算法来优化物理模型.
  • 开发了三种生物启发的协议:内部结合动力学设计,外部子单元定位和中间循环.
  • 在高维参数空间中对速率常数进行数值搜索.

主要成果:

  • 发现各种自组装优化解决方案,包括内部设计,外部定位和回收协议.
  • 内部接口设计解决方案是最有效的,并且使用更多的子单元扩展最好.
  • 外部控制协议 (定位,回收) 即使具有低于最佳的结合动力学,也有效,特别是对于不同的子单元.

结论:

  • 存在多种策略来消除动力陷,并最大限度地提高复杂系统中的组装产量.

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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
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  • 小单元的多样性显著提高了组装效率,特别是与外部控制协议.
  • 这项研究确定了动力捕获成本的普遍缩放规律.