Computational studies of the binding modes of A2A adenosine receptor antagonists

Abstract

A molecular docking study was performed on several structurally diverse A2A AR antagonists, including xanthines, and non-xanthine type antagonists to investigate their binding modes with A2A adenosine receptor (AR), one of the four subtypes of AR, which is currently of great interest as a target for therapeutic intervention, in particular for Parkinson's disease. The high-affinity binding site was found to be a hydrophobic pocket with the involvement of hydrogen bonding interactions as well as π-π stacking interactions with the ligands. The detailed binding modes for both xanthine and non-xanthine type A2A antagonists were compared and the essential features were extracted and converted to database searchable queries for virtual screening study of novel A2A AR antagonists. Findings from this study are helpful for elucidating the binding pattern of A 2A AR antagonists and for the design of novel active ligands. © 2007 Springer-Verlag.