Simulation and Comparative Analysis of Different Binding Modes of Non-nucleoside Agonists at the A2A Adenosine Receptor.

Non-nucleoside agonists of adenosine receptors were analysed at the A2A adenosine receptor to simulate and compare their possible binding modes. The docking studies were performed by using different arrangements of the binding cavity and various docking tools. Mutagenesis results reported in literature were used as reference data for the assessment of the different ligand arrangements observed in this study. The results suggest four possible binding modes, two of which appear compatible with an agonist activity and in agreement with the mutagenesis data. This study provides useful information for the design of new simplified compounds presenting agonist activity at the A2A adenosine receptor.