Use of Metadynamics in the Design of isoDGR-Based αvβ3 Antagonists To Fine-Tune the Conformational Ensemble

Authors

  • Dr. Andrea Spitaleri,

    1. Dulbecco Telethon Institute, Biomolecular NMR Laboratory c/o Center of Genomic and Bioinformatics, S. Raffaele Scientific Institute via Olgettina 58, 20132 Milan (Italy), Fax: (+39) 02-2643-4153
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  • Dr. Michela Ghitti,

    1. Dulbecco Telethon Institute, Biomolecular NMR Laboratory c/o Center of Genomic and Bioinformatics, S. Raffaele Scientific Institute via Olgettina 58, 20132 Milan (Italy), Fax: (+39) 02-2643-4153
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  • Dr. Silvia Mari,

    1. Dulbecco Telethon Institute, Biomolecular NMR Laboratory c/o Center of Genomic and Bioinformatics, S. Raffaele Scientific Institute via Olgettina 58, 20132 Milan (Italy), Fax: (+39) 02-2643-4153
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  • Luca Alberici,

    1. MolMed SpA via Olgettina 58, 20132 Milan (Italy), Fax: (+39) 02-2127-7322
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  • Dr. Catia Traversari,

    1. MolMed SpA via Olgettina 58, 20132 Milan (Italy), Fax: (+39) 02-2127-7322
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  • Dr. Gian-Paolo Rizzardi,

    Corresponding author
    1. MolMed SpA via Olgettina 58, 20132 Milan (Italy), Fax: (+39) 02-2127-7322
    • MolMed SpA via Olgettina 58, 20132 Milan (Italy), Fax: (+39) 02-2127-7322
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  • Dr. Giovanna Musco

    Corresponding author
    1. Dulbecco Telethon Institute, Biomolecular NMR Laboratory c/o Center of Genomic and Bioinformatics, S. Raffaele Scientific Institute via Olgettina 58, 20132 Milan (Italy), Fax: (+39) 02-2643-4153
    • Dulbecco Telethon Institute, Biomolecular NMR Laboratory c/o Center of Genomic and Bioinformatics, S. Raffaele Scientific Institute via Olgettina 58, 20132 Milan (Italy), Fax: (+39) 02-2643-4153
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  • This research was supported in part by a research grant from the Italian Ministry of Research (FIRB). We thank Dan Zhou for technical assistance and Renato Longhi for peptide synthesis. We are grateful to Prof. Wilfred van Gunsteren, Dr. M. Bonomi, F. L. Gervasio, and Dr. A. Barducci for useful discussions.

Abstract

original image

Eine gelungene Kombination: Ein gekoppeltes Metadynamik-/Docking-Verfahren erweist sich als exzellente Technik für den gezielten Entwurf von diagnostischen und therapeutischen Wirkstoffen basierend auf dem isoDGR-Motiv (siehe Bild; FES=Hyperfläche der freien Energie). Das Verfahren könnte auch für andere Ligand-Rezeptor-Systeme genutzt werden.

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