Protein–Protein Docking in Drug Design and Discovery

  • Agnieszka A. KaczorEmail author
  • Damian Bartuzi
  • Tomasz Maciej Stępniewski
  • Dariusz Matosiuk
  • Jana Selent
Part of the Methods in Molecular Biology book series (MIMB, volume 1762)


Protein–protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called “hot spots” in protein–protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein–protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein–protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein–protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein–protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein–protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein–protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

Key words

Drug design and discovery GPCRs Molecular modeling Protein–protein docking Transmembrane proteins Water-soluble proteins 



The chapter was developed using the equipment purchased within the project “The equipment of innovative laboratories doing research on new medicines used in the therapy of civilization and neoplastic diseases” within the Operational Program Development of Eastern Poland 2007–2013, Priority Axis I Modern Economy, operations I.3 Innovation promotion. T.S. and J.S. acknowledge support from Instituto de Salud Carlos III FEDER (CP12/03139 and PI15/00460). A.A.K., T.S. and J.S. participate in the European COST Action CM1207 (GLISTEN). T.S. acknowledges financial support from Hospital del Mar Medical Research Institute.


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

Authors and Affiliations

  • Agnieszka A. Kaczor
    • 1
    • 2
    Email author
  • Damian Bartuzi
    • 1
  • Tomasz Maciej Stępniewski
    • 3
  • Dariusz Matosiuk
    • 1
  • Jana Selent
    • 3
  1. 1.Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modelling LabMedical University of LublinLublinPoland
  2. 2.School of PharmacyUniversity of Eastern FinlandKuopioFinland
  3. 3.GPCR Drug Discovery GroupResearch Programme on Biomedical Informatics (GRIB), Universitat Pompeu Fabra (UPF)-Hospital del Mar Medical Research Institute (IMIM), Parc de Recerca Biomèdica de Barcelona (PRBB)BarcelonaSpain

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