The journal of physical chemistry. B | 2019
Ligand-Dependent Sodium Ion Dynamics within the A2A-Adenosine Receptor: A Molecular Dynamics Study.
Abstract
Sodium ions have long been known reduce the binding of agonists in many class-A GPCRs while having little effect on antagonist binding. Here, using long-timescale classical all-atom molecular dynamics simulations, we explore, in atomic detail, the motion of sodium ions within the ligand-binding pocket of the A2A adenosine receptor (A2A-AR) both in the presence and absence of ligands and in the active and inactive state. We identify novel secondary ion binding sites within the pocket and find that the types of ion motions within the pocket are highly dependent on the presence and type of ligand within the pocket. Our results provide a first step towards developing a molecular understanding of the impact of sodium ions on class-A GPCRs.