3.6.3. PPARδ complexes
CAVITY
RMSD analysis was performed to measure the similarity between two superimposed atomic coordinates. The RMSD analysis for PPARδ complexes showed the mean RMSD for crystal bound ligand Iloprost, FDA-approved drug Lifitegrast and Lanifibranor 1.56 Å, 1.44 Å, and 1.80 Å, respectively (The root-mean-square fluctuation (RMSF) measures the average fluctuations of protein residue over the time course. It measures the deviations of protein residues from a reference position. The mean RMSF for PPARδ in complex with Iloprost and Lifitegrast were same i.e., 0.88 Å whereas the mean RMSF of 0.94 Å was observed for Lanifibranor-PPARδ (In Lifitegrast-PPARδ, the maximum fluctuation of 4.7 Å was shown by residue Lys204, away from the binding pocket. This residue is present at the entrance to the ligand-binding site, it might be crucial in making the ligand intact with the protein by providing flexibility to the overall structure. Other than these sets of residues, the residues of the active site (Ala306-Gly308) were structurally changing from loop to helix and helix to loop during simulation. Asn307 is the most flexible residue it allows the large ligand to enter the ligand-binding cavity [(A) Superimposed structures of pdb of PPARδ-Lanifibranor Complex, Movement of ligand at different time scales during the simulation, and Closer view of conformational changes at H-12. (B) 2D interaction of Lanifibranor with PPARδ at 50-ns time.