Identification of novel multitargeted PPARa/?/d pan agonists by core hopping of rosiglitazone

Wang, Xue-Jiao; Zhang, Jun; Wang, Shu-Qing; Xu, Wei-Ren; Cheng, Xian-Chao; Wang, Run-Ling

In order to study the dynamic details of key residues interacted with the ligand, the root mean square fluctuations (RMSF) of all the side chain residues were obtained. The RMSF curve of PPARs-Cpd#1 complex was similar to that of PPARs-original ligand complex (Figure 4) . At the key residues of PPARα such as Ser280 (the pink area), Tyr314 (the conch area), Tyr464 (the cyan area), and His440 (the coral area), the RMSF values of the PPARα-Cpd#1 complex were somewhat lower than those of the PPARα-original ligand complex and PPARα-apo form. As for PPARγ/δ, similar circumstances existed just as with PPARα. These molecular dynamics simulation trajectories indicated that PPARs became more stable after binding Cpd#1.