Molecular Simulations and Drug Discovery of Adenosine Receptors

Abstract

G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins. Four subtypes of adenosine receptors (ARs), the A1 AR, A2A AR, A2B AR and A3 AR, each with a unique pharmacological profile and distribution within the tissues in the human body, mediate many physiological functions and serve as critical drug targets for treating numerous human diseases including cancer, neuropathic pain, cardiac ischemia, stroke and diabetes. The A1 AR and A3 AR preferentially couple to the Gi/o proteins, while the A2A AR and A2B AR prefer coupling to the Gs proteins. Adenosine receptors were the first subclass of GPCRs that had experimental structures determined in complex with distinct G proteins. Here, we will review recent studies in molecular simulations and computer-aided drug discovery of the adenosine receptors and also highlight their future research opportunities.