Fig. 4.
Ligand activation of precoupled 5-HT2A-Gq protein complex. Gq protein activation mediated by (A) 25CN-NBOH, a full agonist, and (C) LSD, a partial agonist, upon binding to the precoupled 5-HT2A-Gq protein complex. Gq protein inhibited activation caused by (E) absence of an agonist (apo-5-HT2A) and (G) methiothepin, an inverse agonist upon binding to the precoupled 5-HT2A-Gq protein complex. (B, D, F, and H) MetaD free energy of Gαq-bound GDP opening from its GDP binding site. Here, the distance between the AH domain (the center of mass of Cα for the residues 154 to 161 and 175 to 182) and the Ras-like domain (the center of mass of Cα for the residues 51 to 62), was considered for the free energy calculations. The weighted averages and the SDs were calculated for ΔGif for the converged period. The metaD free energies were reweighted (51) for estimation of the error, particularly energy barrier ΔG‡ presented in B, D, F, and H, using the block averaging method.