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Characterization of Ligand Binding to GPCRs Through Computational Methods

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Computational Methods for GPCR Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1705))

Abstract

The recent increase in available G protein-coupled receptor structures now contributes decisively to the structure-based ligand design. In this context, computational approaches in combination with medicinal chemistry and pharmacology are extremely helpful. Here, we provide an update on our structure-based computational protocols, used to answer key questions related to GPCR-ligand binding. All combined, these techniques can shed light on ligand binding modes, determine the molecular basis of conformational selection, for agonists and antagonists, as well as of subtype selectivity. To illustrate each of these questions, we will consider examples from existing projects on three families of class A (rhodopsin-like) GPCRs: one small-molecule (nucleotide-like) family, i.e., the adenosine receptors, and two peptide-binding receptors: neuropeptide-Y and angiotensin II receptors. The successful application of the same computational protocols to investigate this diverse group of receptor families gives an idea of the general applicability of our methodology in the characterization of GPCR-ligand binding.

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Notes

  1. 1.

    During the processing of this manuscript one structure for the AT2 receptor (5UHN) and 2 structures for the A1 adenosine receptor (PDB codes 5N2S and 5UEN) were released.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, Uppsala, SE-751 24, Sweden

    Silvana Vasile, Mauricio Esguerra, Willem Jespers, Ana Oliveira, Jessica Sallander, Johan Åqvist & Hugo Gutiérrez-de-Terán

Authors
  1. Silvana Vasile
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  2. Mauricio Esguerra
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  3. Willem Jespers
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  4. Ana Oliveira
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  5. Jessica Sallander
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  6. Johan Åqvist
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  7. Hugo Gutiérrez-de-Terán
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Correspondence to Hugo Gutiérrez-de-Terán .

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  1. Evotec (UK) Ltd., Abingdon, Oxfordshire, United Kingdom

    Alexander Heifetz

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Vasile, S. et al. (2018). Characterization of Ligand Binding to GPCRs Through Computational Methods. In: Heifetz, A. (eds) Computational Methods for GPCR Drug Discovery. Methods in Molecular Biology, vol 1705. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7465-8_2

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  • DOI: https://doi.org/10.1007/978-1-4939-7465-8_2

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7464-1

  • Online ISBN: 978-1-4939-7465-8

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