Additional insights into Key Determinants for Adenosine 1 Receptor Antagonists Selectivity using Supervised Molecular Dynamics Simulations

<p>Adenosine receptors (ARs), like many other G protein-coupled receptors (GPCRs), are targets of primary interest in drug 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 done for clarifying the selectivity on 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 A_2AAR antagonist investigating their recognition trajectories obtained by Supervised Molecular Dynamics from unbound state and monitoring the role of the water molecules in the binding site.</p>