SUPPLEMENTARY MATERIAL

For the article:

Molecular requirements involving the human platelet protease-

activated receptor-4 mechanism of activation by peptide

analogues of its tethered-ligand

By Moschonas et al.

Figure S1. A. Sequence alignment between PAR-1 and PAR-4 as predicted using Prime (in

red are shown the conserved residues); B. Ramachandran plot for the resulting homology

model (favorable region is shown in green, allowed region in blue and disallowed region in

red);

Figure S2. Predicted cavities as possible binding sites in PAR-4 revealed using SiteID.

Figure S3: Three-dimensional and two-dimensional docking pose of the Ac-AYPGKF-NH2

peptide in the PAR-4 structure.

Figure S4: Three-dimensional and two-dimensional docking pose of the trans-cinnamoyl-

AYPGKF-NH2 peptide in the PAR-4 structure.

Figure S5: Three-dimensional and two-dimensional docking pose of the YPGKF-NH2

peptide in the PAR-4 structure.

Figure S6: Three-dimensional and two-dimensional docking pose of the Ac-YPGKF-NH2

peptide in the PAR-4 structure.

Figure S7: Three-dimensional and two-dimensional docking pose of the caffeoyl-YPGKF-

NH2 peptide in the PAR-4 structure.

Figure S8: Three-dimensional and two-dimensional docking pose of YD-3 in the PAR4

structure.

Figure S9: Three-dimensional and two-dimensional docking pose of ML-354 in the PAR-4

structure.

Figure S10: Three-dimensional and two-dimensional docking pose of BMS-986120 in the

PAR-4 structure.

Figure S11: Superposition of the docking poses of the three small molecules [A. YD-3; B.

ML-354; C. BMS-986120 (shown in purple)] that act as antagonists for PAR-4 and the

docking pose of trans-cinnamoyl-YPGKF-NH2 (shown in green). The most important

residues involved in the binding of both the peptide and the small molecules are shown in

gray color.