Computer aided comparative analysis of the binding modes of the adenosine receptor agonists for all known subtypes of adenosine receptors

Molecular models of all known subtypes (A(1), A(2A), A(2B), and A(3)) of the human adenosine receptors were built in homology with bovine rhodopsin. These models include the transmembrane domain as well as all extracellular and intracellular hydrophilic loops and terminal domains. The molecular docking of adenosine and 46 selected derivatives was performed for each receptor subtype. A binding mode common for all studied agonists was proposed, and possible explanations for differences in the ligand activities were suggested. (c) 2006 Elsevier Inc. All rights reserved.