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Smadbeck, J., Peterson, M. B., Khoury, G. A., Taylor, M. S., Floudas, C. A. Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules. J. Vis. Exp. (77), e50476, doi:10.3791/50476 (2013).

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デノボタンパク質設計の目的は、天然の配列に対して、例えば結合親和性、アゴニストまたはアンタゴニストの動作、又は安定性などの特定の性質、所望の改善を持つ3次元構造に折り畳まになるアミノ酸配列を見つけることである。タンパク質の設計には、現在の進歩の薬物設計と発見の中心に位置しています。だけでなく、タンパク質の設計は潜在的に有用な薬物標的の予測を提供し、それはまた、タンパク質の折り畳みプロセスおよびタンパク質 - タンパク質相互作用の理解を高めるない。このような定方向進化のような実験方法は、タンパク質の設計の成功を示している。しかし、そのような方法はtractably検索できる限られた配列空間によって制限されています。対照的に、計算設計戦略は、特性及び機能の様々な被覆配列の非常に大きなセットのスクリーニングを可能にする。我々は、計算のde novoタンパク質設計メトキシの範囲を開発しているタンパク質設計のいくつかの重要な分野に取り組むことのできるDS。これらには、増大した結合親和性のために増加した安定性との複合体のための単量体のタンパク質の設計が含まれています。

より広範な使用のためのこれらの方法我々現在のタンパク質WISDOM(普及にhttp://www.proteinwisdom.org )、タンパク質設計に関するさまざまな問題のために自動化された方法を提供するツールです。構造テンプレートは、設計プロセスを初期化するために提出されます。設計の第一段階は、シーケンス空間にポテンシャルエネルギーの最小化を介して安定性を改善することを目的とする最適化シーケンスを選択する段階である。選択された配列は、その後、折り目特異ステージと結合親和性の段階を介して実行されています。プロセスの各ステップのための配列のランク順序付きリストは、関連する設計された構造に加えて、設計の包括的な定量的評価をユーザに提供します。ここでは詳細をOを提供fは、それぞれ設計方法、並びに方法の使用によって達成いくつかの注目すべき実験成功。


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