New Insights into Key Determinants for Adenosine 1 Receptor Antagonists Selectivity Using Supervised Molecular Dynamics Simulations

Giovanni Bolcato, Maicol Bissaro, Giuseppe Deganutti, Mattia Sturlese, Stefano Moro

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Abstract

Adenosine receptors (ARs), like many otherGprotein-coupledreceptors (GPCRs), are targets of primary interest indrug design. However, one of the main limits for the development of drugs for this class of GPCRs is the complex selectivity profile usually displayed by ligands. Numerous efforts have been madefor clarifying the selectivity of ARs, leading to the development of many ligand-based models. The structure of the AR subtype A1 (A1AR) has been recently solved, providing important structural insights. In the present work, we rationalized the selectivity profile of two selective A1AR and A2AAR antagonists, investigating their recognition trajectories obtained by Supervised Molecular Dynamics from an unbound state and monitoring the role of the water molecules in the binding site.
Original languageEnglish
Article number732
Number of pages11
JournalBiomolecules
Volume10
Issue number5
DOIs
Publication statusPublished - 7 May 2020
Externally publishedYes

Bibliographical note

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Keywords

  • GPCRs
  • adenosine receptorss
  • selectivity
  • A1AR; A2AAR
  • antagonist
  • moleculardynamics (MD);
  • supervised molecular dynamics (SuMD)

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