3.6.2. PPARγ complexes
To measure the deviation and conformation stability of backbone atoms the RMSD of all PPARγ complexes were computed. Average RMSD of protein elucidates the stability of the structure and it is also an important indicator of the biological process. The mean RMSD value of Raltitrexed-PPARγ and Lanifibranor-PPARγ complexes were 1.8 Å and 1.7 Å respectively ((A) Superimposed structures of pdb of Raltitrexed-PPARγ Complex at 0-ns (lime green), 110-ns (dodger blue), 184-ns (orchid), and 200-ns (gold), and closer view of conformational shift and Raltitrexed movement.The Lanifibranor-PPARγ complex shows the stable RMSD plot. The pentanoic acid group of Lanifibranor constantly changed its interacting residues. At the beginning of the simulation, the 5-chloro-1H-indole group was interacting with Gln80, His243, Leu247, and Leu263 and the pentanoic acid was interacting with Phe76 and Phe154. At 80ns, Cys79, Phe76, and His243 engaged with the 5-chloro-1H-indole group, whereas Phe154 formed a hydrogen bond with pentanoic acid. During simulation, the ligand structure compacted, bringing the pentanoic acid and benzo[d]thiazole rings closer. At the end of the simulation, residues Cys79 were interacting with both the 5-chloro-1H-indole group and the benzo[d]thiazole group. Lys161 made contact with the 5-chloro-1H-indole group and sulfur dioxide which linked both these groups. Ile120 was seen interacting with the benzo[d]thiazole group whereas no residue was seen interacting with pentanoic acid ((A) Movement of Lanifibranor in PPARγ at different time scales. (B) 2D interaction diagram of Lanifibranor at 200ns with interacting residues of PPARγ.The majority of subtle conformational changes in PPARγ complexes were seen within the loop (Gly33-Asp45) and Ω-loop (Lys55-Glu70). The fluctuations in H-12 were detected during trajectory analysis. This might be due to the ligand’s lack of direct interaction with H-12. The mean RMSF of 1.10 Å and 0.97 Å were calculated for Raltitrexed-PPARγ and Lanifibranor-PPARγ, respectively. The ligands were interacting with the residues of Arm II and Arm III. Both ligands bind to PPARγ and partially activate it.