3.4.1. Crystal ligands docking
The performance of the docking algorithm is evaluated by redocking the ligands using the conformations discovered in the X-ray structures. The crystal ligands APHM13, Lanifibranor, and Iloprost successfully docked back to PPARα, PPARγ, and PPARδ in their binding pockets showing the LibDockScore of 155.849, 104.357, and 128.873, respectively. The RMSD between docked pose and crystallographic pose of APHM13:PPARα and Lanifibranor: PPARγ were 0.477 Å and 0.392 Å, respectively, due to a subtle difference in the binding residues but for Iloprost: PPARδ RMSD of 0.00 Å was observed. Upon 2D interaction analysis using DS, it was revealed that residues Ile76, Cys79, Cys80, Leu125, Val136, and Ala137 of PPARα were the common residues forming interaction with APHM13 in both docked complex and crystallographic complex. In addition to this, APHM13 also contacted with PPARα other residues: Val59, Ser84, Ile143, Tyr118, His244, and Tyr268 in crystallographic complex whereas in docked complex the additional residues that showed interaction were: Asn23, Met24, Glu90, Met124, and Val128of PPARα. The 3D interaction diagram of APHM13 in crystal pose and docked pose is illustrated in The superimposed crystallographic pose (receptor in light sea green and ligand in dark green) and docked pose (receptor in hot pink and ligand in orange) of (A) PPARα, (B) PPARγ and (C) PPARδ. Helix-12 is represented in yellow.The Lanifibranor showed interaction with residues of PPARγ: Cys79, Arg82, Tyr121, Leu124, Phe157, Met158, and Ser183 in both complexes. Moreover, some residues Phe76, Ile120, Phe154, and Lys161 of PPARγ were also involved in interaction in docked complex instead of residues Gly78 and Ile135 which were engaged in interaction with Lanifibranor in the crystallographic complex (In docked complex, the interaction between Iloprost and PPARδ included the involvement of residues Cys77, Thr80, Thr81, His115, Ile118, Phe119, leu122, Ile156, Lys159, His241, and Tyr265 which were all also making interactions in crystal complex although some additional residues Leu47, Val73, Cys76, Val133, and Val140 were also observed interacting with Iloprost in crystal complex (