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関連する概念動画

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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関連する実験動画

Updated: Jun 30, 2026

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

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

Published on: September 27, 2013

関連する正常モードを通じたリガンドドッキングにおける受容体の柔軟性を表しています.

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
まとめ
この要約は機械生成です。

この研究は,薬剤開発における受容体の柔軟性をモデル化するための新しい正常モード法を導入しています. このアプローチは,リガンドドッキングの精度を高め,多様な受容体構成を生成することによって,仮想スクリーニングを改善します.

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関連する実験動画

Last Updated: Jun 30, 2026

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

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

Published on: September 27, 2013

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08:44

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科学分野:

  • コンピュータ生物学 コンピュータ生物学
  • 構造生物学 構造生物学とは
  • ドラッグ・ディスカバリー・ドリッグ・ディスカバリー・ドリッグ・ディスカバリー・ドリッグ・ディスカバリー

背景:

  • リンガンド受容体相互作用は,薬剤発見において極めて重要です.
  • 既存のドッキング方法は,しばしば受容体の柔軟性を正確に表現するのに苦労します.
  • タンパク質の柔軟性,特に結合ポケットの柔軟性は,リガンド結合親和性に大きく影響する.

研究 の 目的:

  • リガンドドッキングと仮想スクリーニングに受容体の柔軟性を組み込むための正常モードベースの方法論を開発する.
  • 複雑なタンパク質の変形を表現する現行の方法の限界に対処する.
  • 構造ベースの薬剤発見ツールの正確性と効率性を向上させる.

主な方法:

  • 重要な柔軟性モードを特定するために,通常のモードの関連性測定法を導入しました.
  • 関連する正常モードに沿って混乱することによって,受容体構成のアンサンブルを生成します.
  • 仮想スクリーニングのためのフルフレキシブルドッキングとレセプターアンサンブルドッキングを使用しています.
  • cAMP依存タンパク質キナーゼのホロおよびアポ構造に関する方法を評価した.

主要な成果:

  • この方法は,限られた数の低周波モードを使用して,cAMP依存タンパク質キナーゼのループの柔軟性を効果的に捉えます.
  • ドッキング精度は向上し,リガンドはターゲット構造から1.5 Å以内で達成しました.
  • 仮想スクリーニングのパフォーマンスは向上し,強化された濃縮因数によって示されました.
  • 結合物質と非結合物質の差別が改善されたことを実証した.

結論:

  • 開発された通常のモードのアプローチは,柔軟なリガンド-柔軟な受容体ドッキングを体系的に統合しています.
  • この方法論は,構造ベースの薬剤発見の重要な進歩を表しています.
  • このアプローチは,計算によるスクリーニングにおけるタンパク質の柔軟性のより現実的なモデリングを提供します.