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Approaches for Differentiation and Interconverting GPCR Agonists and Antagonists

  • Przemysław Miszta
  • Jakub Jakowiecki
  • Ewelina Rutkowska
  • Maria Turant
  • Dorota Latek
  • Sławomir Filipek
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1705)

Abstract

Predicting the functional preferences of the ligands was always a highly demanding task, much harder that predicting whether a ligand can bind to the receptor. This is because of significant similarities of agonists, antagonists and inverse agonists which are binding usually in the same binding site of the receptor and only small structural changes can push receptor toward a particular activation state. For G protein-coupled receptors, due to a large progress in crystallization techniques and also in receptor thermal stabilization, it was possible to obtain a large number of high-quality structures of complexes of these receptors with agonists and non-agonists. Additionally, the long-time-scale molecular dynamics simulations revealed how the activation processes of GPCRs can take place. Using both theoretical and experimental knowledge it was possible to employ many clever and sophisticated methods which can help to differentiate agonists and non-agonists, so one can interconvert them in search of the optimal drug.

Key words

GPCRs Agonists Activation Ligand docking Fingerprints Molecular dynamics 

Notes

Acknowledgments

Figure 3 is reproduced from J. Chem. Inf. Model. 2015 (http://pubs.acs.org/doi/full/10.1021/acs.jcim.5b00066) with permission from American Chemical Society. Figure 9 is reproduced from ACS Chem. Biol. 2013 (http://pubs.acs.org/doi/full/10.1021/cb400103f) with permission from American Chemical Society. Figure 18 is reproduced from FEBS Lett. 2015 with permission from John Wiley and Sons.

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Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  • Przemysław Miszta
    • 1
  • Jakub Jakowiecki
    • 1
  • Ewelina Rutkowska
    • 1
  • Maria Turant
    • 1
  • Dorota Latek
    • 1
  • Sławomir Filipek
    • 1
  1. 1.Biological and Chemical Research Centre, Faculty of ChemistryUniversity of WarsawWarsawPoland

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