As a negative control, the similar molecular dynamics simulation was also performed for Comp#8 (A-B2-C3), which is ranked number 25 according to the strength of binding affinity with PPARa and PPARc (cf. Table 1 ). The corresponding simulation results thus obtained are shown in the Fig. 4 , from which we can see that the fluctuating magnitudes of molecular dynamics for PPARa-Comp#8 and PPARc-Comp#8, including the RMSD and RMSF, are much larger than those of PPARa-Comp#1 and PPARc-Comp#1, especially for the binding site of AF2 helix region (see the gray frames in Fig. 4B and D) . These phenomena indicate that Comp#8 is not as good as Comp#1 in stably binding to PPARa and PPARc, and hence Comp#8 might not have the same function for activating the AF2 helix as GW409544 had.