Figure 4.

Vorapaxar interactions in the TM4–TM5 metastable state. (A) Extracellular view of the PAR1–vorapaxar crystal structure. Labeling is identical to that in Figure 3. The ethyl carbamate moiety of vorapaxar is indicated by an arrow. (B–D) Representative poses from the three simulations in which vorapaxar dissociated from PAR1 through the TM4–TM5 tunnel. The residues and lipids that interact most frequently with vorapaxar in the metastable state are colored according to a heat map, from the most frequently interacting (dark red) to the ninth most frequently interacting (dark blue). Ballesteros–Weinstein numbering is indicated by superscripts. Plots of the displacement of the vorapaxar COM from the crystallographic position vs simulation time are shown at the bottom right of each panel. The metastable state is indicated by vertical dashed lines.