Figure 6.

Effect of Na⁺ Ions in Diverse Conformational States

Effect of Na⁺ ion in the MD simulations of the inverse agonist ZM241385-bound inactive state R (R_ZMA241385/Na), agonist NECA-bound inactive state R (R_NECA/Na), active-intermediate state R′ (R′_NECA/Na), and G protein-bound fully active state R^∗·G (R^∗·G_NECA/Na). The Na⁺ ion retains the hydrogen bonds with residues D52^2.50 and S91^3.39 and a water-mediated hydrogen bond with W246^6.48 during the MD simulations of ZM241385-bound R state and as seen in the crystal structure of ZM241385-bound inactive state of A_2AR (PDB: 4EIY). Agonist NECA binding in the R′ and R^∗·G states disrupts the interaction of the Na⁺ with S91^3.39 but retains the interaction with D52^2.50. The waters present in the ZM241385-bound R state rearrange in the agonist-bound simulations.