オーダーされたペプチドマクロサイクルの包括的な計算設計
Parisa Hosseinzadeh1, Gaurav Bhardwaj1, Vikram Khipple Mulligan1
1Department of Biochemistry and Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Science (New York, N.Y.)
|December 16, 2017
まとめ
研究者は新しい混合キラリティペプチドマクロサイクルを設計するための計算方法を開発しました. このアプローチは 薬の発見と治療開発に利用できる 構造的多様性を大きく拡大します
科学分野:
- 薬剤化学
- コンピュータ化学
- 構造生物学
背景:
- シクロスポリンのような混合キラリティペプチドマクロサイクルは強力な治療薬である.
- 既存の方法は,これらの化合物の構造的多様性を調査するための体系的なアプローチを欠いています.
- 自然なタンパク質は新しいペプチドマクロサイクルを設計するための貧しいテンプレートです.
研究 の 目的:
- 混合キラリティペプチドマクロサイクルの安定した構造を数え出すための計算戦略を開発する.
- 新薬開発のためのペプチドマクロサイクルの設計
- 実験的な構造で計算上の予測を検証する.
主な方法:
- マクロサイクリックペプチドのほぼ完全な骨格採取.
- シーケンス設計とエネルギー環境の計算
- 核磁共振 (NMR) 構造の決定
主要な成果:
- 単一の安定した構造を採用すると予測された200以上の設計マクロサイクルを特定しました.
- 設計されたマクロサイクルの実験構造は,計算モデルと密接に一致しました.
- 利用可能なペプチドマクロサイクル・スキャフォールドの有意な拡張を示した.
結論:
- 開発された計算方法は,短ペプチドマクロサイクル構造空間を包括的にカバーします.
- 薬剤の合理的な設計と 図書館の選択のための スタート地点を大きく増やします
- 新しい治療ペプチドマクロサイクルの体系的な探査と設計を可能にします.
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