Figure 3.

Vorapaxar interactions in the TM6–TM7 metastable state. (A) Extracellular view of the PAR1–vorapaxar crystal structure. TMs are shown as cylinders and labeled 1–7. Vorapaxar is shown as spheres, and the ethyl carbamate moiety is indicated by an arrow. (B–F) Representative poses from the five simulations in which vorapaxar dissociated from PAR1 through the TM6–TM7 tunnel. The amino acid residues and POPC molecules 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). Amino acids are rendered as balls and sticks, and lipids are rendered as sticks. 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.