Figure 1.

Conformational Sampling of A_2AR Bound to NECA in Four Different States

(A) Conformational ensembles from the MD simulations clustered by comparisons of the distances between TM3-TM6 and TM3-TM7. MD ensembles for A_2AR bound to NECA in four different states were projected on to these two distances and contour maps plotted for the C_α-C_α distances of R102^3.50-E228^6.30 and R102^3.50-Y288^7.53. The numbers 1, 2, and 3 in the figures correspond to the C_α-C_α distances in the crystal structures of inactive (PDB: 3PWH, number 1), active-intermediate (PDB: 2YDV, number 2), and the mini-Gs-bound fully active state of A_2AR (PDB: 5G53, number 3).

(B) Representative structures extracted from the most populated cluster of A_2AR bound to the agonist NECA in the inactive state (R_NECA), the active-intermediate state (R′_NECA), and the fully active G protein-bound state (R^∗·G_NECA). The R^∗·G⁻_NECA state is a metastable state observed upon MD simulation of the receptor after removal of the G protein. The color scheme ranges from red to blue, with blue indicating low flexibility and red high flexibility. The flexibility is quantified by the B factor calculated from root-mean-square fluctuation in Å.