It is instructive to point out that the RMSF curve of PPARa-Comp#1 or PPARc-Comp#1 is highly similar to that of PPARa-GW409544 or PPARc-GW409544, respectively. This is especially remarkable in the binding site of AF2 helix region with the residues 459-465 for PPARa-Comp#1 and residues 469-477 for PPARc-Comp#1 (see the grey frames in Fig. 3B and D) , indicating that the new designed compound, Comp#1, is very likely to have the same function for activating the AF2 helix as done by GW409544.