Computational Modeling of Trans-Zeatin as a Novel Target of Adenosine A2A Receptor: Insights into Molecular Interactions

Abstract

Background: Adenosine A2A receptor (A2AR) is a G-protein-coupled receptor that is involved in various physiological functions. Zeatin, a plant cytokinin and a derivative of adenine, is recently identified as new ligand of A2AR. However, the ligand-receptor interaction mechanism is not fully revealed. Aims and Objectives: The main aim of this study is to reveal a model structure of A2AR in complex with zeatin for the first time to provide a better understanding of this novel interaction mechanism. Materials and Methods: The model structure of A2AR in complex with zeatin was created by docking and the structural dynamics of the complex were detected by molecular dynamic simulations during the study. A model structure of A2AR in complex with caffeine was used as a positive control. Result: Zeatin displayed the ability to stay more stable at the binding pocket compared with caffeine based on molecular dynamic simulations and the residues involved in the interaction are identified, leading a new sight for further studies on zeatin and A2AR interaction. Conclusion: We propose that zeatin is indeed a novel and promising target for A2AR.