Extended Data Fig. 6: MD simulations of iperoxo and DCZ in WT and DREADD receptors.
From: Molecular basis for selective activation of DREADD-based chemogenetics
a, Activation of hM4R and hM4R (A203G) under the stimulation of iperoxo by the BRET assay. See Supplementary Table 10 for fitted parameter values that represent mean ± SEM of n = 4 biologically independent experiments. b-c, Basal activities of hM3Dq (b) and hM4Di (c) by BRET2 assay. Data represent the mean ± SEM. ***p = 0.0004 (hM3Dq, n = 6), ****p < 0.0001 (hM4Di, n = 6), unpaired two-tailed student t-test. d-e, Interaction between W4x57 and N3x37 at the start and end snapshots of the simulation of hM3Dq-iperoxo (d) and hM3R-iperoxo (e). f-g, Representative poses of iperoxo (f) and DCZ (g) in the hM3R (A5x461G) and hM3Dq (G5x461A) during the MD simulation, respectively. h—m, Statistics analysis of the iperoxo-N153 distance (isoxazole oxygen of iperoxo to ND2 of N153) and W200-N153 distance (indole N of W200 to OD1 of N153) in the simulation of hM3R-iperoxo (h and i), hM3Dq-iperoxo (j and k), and hM3R (A5x461G)-iperoxo (l and m), respectively. n-o, Statistics analysis of the DCZ-D148 distance [nitrogen on the piperazine ring (N02) of DCZ to OD2 of D148] in the simulation of hM3Dq-DCZ (n) and hM3Dq (G5x461A)-DCZ (o), respectively. The x-axis represents the binned distance and the y-axis is the count of frames from the simulations. Each color represents separate runs from the respective simulations.
