Fig. 4: Simulation prevalence of NCoR to PPARγ binding correlates with experiment.
From: Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ
a The prevalence of the indicated hydrogen and salt bridge bonds in individual 1μs conventional MD runs of representative structures from low energy wells (black circles) and the overall Boltzmann weighted average (pink) for the indicated complexes. b Boltzmann average prevalence of hydrogen bonding between the helix 3 charge clamp residue (K329) and NCoR and between a helix 4 residue (N340) and NCoR is shown. The average and standard deviation of these 4 values are shown (0.23 ± 0.005 and 0.55 ± 0.16). p = 9E−3; 95% CI for difference magnitude is 0.1–0.5; t = 3.8; df = 6; unpaired two-tailed t test. c The average decrease in affinity is greater for a mutation abolishing the helix 3 charge clamp (K329A) than for one abolishing the helix 4-NCoR bonding (N340A). The average and standard deviation of these 4 values are (1.4 ± 0.14 and 7.3 ± 1.18). p = 6E−5; 95% CI for difference magnitude is 4.4–7.4; t = 9.92; df = 6; unpaired two-tailed t test. These data are also presented in Supplementary Fig. 11. Each open circle represents the average Kd of the indicated mutant from two independent experiments divided by the average Kd of wt from four independent experiments for apo and PPARγ LBD bound to T0070907, SR10221, or GW9662. Source data are provided as a Source Data file (Source data_Heidari.xlsx).
