Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties
Figure 6
Comb-ED analysis of the conformational spaces visited by 5-HT2AR bound to 5-HT, LSD and KET.
(A) Projections along the first and second eigenvectors obtained from the Comb-ED analysis on the concatenated 5-HT-LSD (upper panel), 5-HT-KET (middle panel), and LSD-KET (lower panel) trajectories. The centers of the conformational space sampled by ligands are in black dots and are connected by black dotted lines. (B) Extreme projections along the first eigenvector of the combined 5-HT-LSD (top panel), 5-HT-KET (middle panel) and LSD-KET (bottom panel) trajectories. The receptor is rendered and colored as in Figure 5B. (C) Comparison of the 5-HT2AR structures in complex with 5-HT, LSD or KET averaged over the final 100 ns aligned with seven most conserved residues in each TM [18]. The receptor structures in complex with different ligands are shown in cartoon and are colored as in panel A.