Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties
Figure 5
Characteristic dynamics of 5-HT2AR induced by 5-HT are reversed by KET.
(A) Evolution of the TM backbone RMSD of KET-substituted receptor compared to KET-bound receptor, averaged along 250–350 ns (top), the minimum distance between the carboxylate oxygens of D3.49 and the guanidine nitrogens of R3.50 (middle), as well as the Cα distance between R3.50 and E6.30 (bottom). (B) Extreme projections along the first eigenvector from Comb-ED analysis of the combined 5-HT-bound and KET-substituted receptors (left panel), as well as KET-bound and KET-substituted (right panel) trajectories. The receptor is shown in tubes, and colors depict magnitudes of conformational changes from small to large (from blue to green, and to red).