Fig. 2: Extensive aMD simulations indicate a diverse PPARγ structural ensemble.
From: Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ
Multiple independent aMD simulations were run for the indicated PPARγ LBD complexes (see Supplementary Table 5). a, d The RMSD of helix 12 was calculated compared to active (chain A) and inactive (chain B) structures (PDB code: 1PRG). The energy of each trajectory snapshot was calculated and overlaid on the 2D RMSD to produce the displayed potential energy landscapes. b, e The aMD trajectory structures within a 0.2 × 0.2 Å RMSD square centered on the lowest energy wells (white circles in panels (a) and (d)) were clustered using k-means clustering into 5 clusters using CPPTRAJ81. Arbitrary (i.e., CPPTRAJ chosen) representative structures are shown for the most prevalent clusters. The relative prevalence of the structure is indicated by the color of helix 12 ranging from dark green for the most prevalent to olive drab, light green, light blue, and then deep sky blue for the least prevalent. For reference, an active structure (rosiglitazone bound PPARγ; 2PRG chain A) is shown with helix 12 colored dim gray. c Representative structures from the third and second lowest energy wells in the inactive and active apo simulations, respectively, are shown in orange and dark green. Active and inactive crystal structures are shown in dim gray and light pink, respectively.
