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相关概念视频

Gap Junctions01:37

Gap Junctions

Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Gap Junctions01:27

Gap Junctions

The cytoplasm of adjacent animal cells can exchange small molecules, ions, and secondary messengers via the communication channels which form the gap junctions. These junctions comprise a few hundred to thousands of molecular channels, each made of two halves, called the connexon hemichannel. A connexon is a hexamer of six transmembrane connexin proteins, which assemble radially, thus forming a pore or channel in the center. One connexon hemichannel docks with a corresponding connexon on the...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...

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相关实验视频

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Insertion of Flexible Neural Probes Using Rigid Stiffeners Attached with Biodissolvable Adhesive
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Insertion of Flexible Neural Probes Using Rigid Stiffeners Attached with Biodissolvable Adhesive

Published on: September 27, 2013

代表受体灵活性在通过相关的正常模式的连接器对接.

Claudio N Cavasotto1, Julio A Kovacs, Ruben A Abagyan

  • 1Molsoft LLC, 3366 North Torrey Pines Court, Suite 300, La Jolla, California 92037, USA. claudio@molsoft.com

Journal of the American Chemical Society
|June 30, 2005
PubMed
概括

这项研究引入了一种新的正常模式方法,用于模拟药物发现中的受体灵活性. 这种方法提高了连接器对接的准确性,并通过生成多种不同的受体构造来改善虚拟选.

科学领域:

  • 计算生物学 计算生物学
  • 结构生物学 结构生物学
  • 药物发现 药物发现 药物发现

背景情况:

  • 体受体相互作用在药物发现中至关重要.
  • 现有的对接方法往往难以准确地代表受体的灵活性.
  • 蛋白质的灵活性,特别是结合口袋中的灵活性,显著影响了连接体结合亲和力.

研究的目的:

  • 开发一种基于正常模式的方法,用于将受体灵活性纳入连接体对接和虚拟选.
  • 解决现有方法在表示复杂蛋白质变形方面的局限性.
  • 提高基于结构的药物发现工具的准确性和效率.

主要方法:

  • 引入了正常模式的相关性指标,以确定关键的灵活性模式.
  • 通过沿着相关的正常模式扰动产生了一组受体构造.
  • 采用完全灵活的对接和接收器组合对接,用于虚拟选.
  • 评估了对cAMP依赖的蛋白质激酶全和 Apo 结构的方法.

主要成果:

  • 该方法有效地捕捉了cAMP依赖蛋白激酶的循环灵活性,使用有限数量的低频模式.
  • 对接精度得到了改进,配体在目标结构的1.5 Å内实现了对接.

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相关实验视频

Last Updated: Jun 30, 2026

Insertion of Flexible Neural Probes Using Rigid Stiffeners Attached with Biodissolvable Adhesive
06:40

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Published on: September 27, 2013

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Rewiring Neuronal Circuits: A New Method for Fast Neurite Extension and Functional Neuronal Connection

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  • 虚拟选的性能得到了提高,通过改进的丰富系数表明了这一点.
  • 证明了结合剂和非结合剂之间的歧视有所改善.
  • 结论:

    • 开发的正常模式方法系统地整合了灵活的连接器-灵活的受体对接.
    • 这种方法代表了基于结构的药物发现的重大进步.
    • 该方法在计算查中提供了更现实的蛋白质灵活性建模.