Molecular Simulations and Drug Discovery of Adenosine Receptors

G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins. Four subtypes of adenosine receptors (ARs), the A(1)AR, A(2A)AR, A(2B)AR and A(3)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 A(1)AR and A(3)AR preferentially couple to the G(i/o) proteins, while the A(2A)AR and A(2B)AR prefer coupling to the G(s) 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.

Automated summary

G protein-coupled receptors (GPCRs) are the largest family of human membrane proteins, with adenosine receptors (ARs) having four subtypes that mediate various physiological functions and serve as drug targets. Adenosine receptors have different coupling preferences with G proteins, leading to future research opportunities in drug discovery.