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Dynamic Undocking: A Novel Method for Structure-Based Drug Discovery

  • Maciej Majewski
  • Sergio Ruiz-Carmona
  • Xavier Barril
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1824)

Abstract

Computer-aided methods have been broadly used in pharmaceutical research to identify potential ligands and design effective therapeutics. Most of the approaches rely on the binding affinity prediction and approximate thermodynamic properties of the system. Our alternative approach focuses on structural stability, provided by native protein–ligand interactions, in particular hydrogen bonds. Based on this idea, we designed new fast computational method, called dynamic undocking (DUck), that evaluates stability by calculating the work necessary to break the most important native contact in a ligand-receptor complex. This property is effective in distinguishing true ligands from decoys and is orthogonal to currently existing docking methods, thus making it exceptionally useful in virtual screening. Here, we present a protocol suitable for DUck’s application in drug design strategy, as well as notes that will help to solve common problems addressed by users.

Key words

Drug discovery Molecular docking Molecular dynamics Structure-based drug design Virtual screening Hydrogen bonds Structural stability 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Maciej Majewski
    • 1
  • Sergio Ruiz-Carmona
    • 1
  • Xavier Barril
    • 1
    • 2
  1. 1.Institut de Biomedicina de la Universitat de Barcelona (IBUB) and Facultat de Farmàcia Universitat de BarcelonaBarcelonaSpain
  2. 2.Catalan Institution for Research and Advanced Studies (ICREA)Passeig Lluís Companys 23BarcelonaSpain

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