## 3 Results and Discussion
### Binding Interaction Analysis with PLIP
#### 3.5.2 Interactions with PPAR-\(\alpha\)
Twelve hydrogen bonds occurred, with new ones including those with Asn219A, Asn236A, Thr279A, Asn336A, and Arg692B. \(\pi\)-stacking with Tyr334A and salt bridges with His257A and His457A were also observed. CSAMut2 on the other hand, as shown in Figure 5j and Supplementary information Table S5j, showed only six hydrophobic interactions and eight hydrogen bonds. \(\pi\)-stacking with His457A and a \(\pi\)-cation interaction with Arg692B were again seen. GLA-Mut2 (Figure 5k and Supplementary information Table S5k), showed increased H-bonds (fourteen hydrogen bonds) and seventeen hydrophobic interactions. New H-bonds were seen with Met220A, Ile272A, His274A, Cys276A, Cys278A, Thr285A, Glu286A, and Leu331A. New hydrophobic interactions were observed with Leu247A, Leu254A, Val255A, Ile272A, Val324A, and Ile339A. \(\pi\)-stacking was observed with Tyr334, while a salt bridge was formed with His457. RMAMut2 (Figure 5l and Supplementary information Table S5l), showed however showed only nine hydrophobic interactions and eight H-bonds. CGAMut3 (Figure 5m and Supplementary Information Table S5m), showed ten hydrophobic interactions including new ones with Lys224A, Ile228A, Leu254A, Val281A, and Glu282A. Eleven hydrogen bonds were seen, new ones occurring with Ser234A, Cys257A, Asn226A, His457A, and Arg692B. The CSAMut3 conjugate shown in Figure 5n and Supplementary Information Table S5n, exhibited twelve hydrophobic interactions, including those with Asn219A, Lys224A, Val227A, Ile228A, Asn236A, and Lys257A. Eight H-bonds were seen, \(\pi\)-stacking was once again seen with Tyr334A, and a \(\pi\)-cation interaction with Lys224A was observed. GLAMut3 (Figure 5o and Supplementary Information Table S5o), showed only six H-bonds with His274A, Thr279A, Glu282A, Thr285A, His457A, and Arg692B. Of the total of nine hydrophobic interactions, new ones were seen with Lys257A, Thr279A, Val281A, Glu282A, His457A, and Leu 693B. \(\pi\)-stacking was observed with His274A and a salt bridge was observed with Arg692B. RMAMut3 (Figure 5p and Supplementary Information Table S5p) displayed eleven hydrophobic interactions, including new ones with Leu254A, Lys257A, Leu258A, Thr279A, Val281A, and Glu282A. Thirteen H-bonds were shown, including new ones with Ala250A, Ala256A, Lys257A, Thr283A, Thr285A, His457A, and Arg692B. Three \(\pi\)-stacking interactions were seen with Tyr334A and one with His457A, while a salt bridge was formed with Arg692B. The CGAMut4 conjugate (Figure 5q and Supplementary Information Table S5q) displayed lesser hydrophobic interactions (seven) with Met220A, Thr279A, Val281A, Tyr334A, Pro458A, and Ile689B but higher H-bonds (sixteen), including new ones with Asn219A, Met220A, Leu254A, Glu282A, Thr285A, Glu286A, His457A, and Arg692B. \(\pi\)-stacking with Tyr334A was shown, as was a salt bridge with His274A. CSAMut4 (Figure 5r and Supplementary Information Table S5r) displayed nine hydrophobic interactions and twelve H-bonds, including new hydrophobic interactions with Val223A, Arg226A, Val227A, Ile228A, Leu229A, Lys232A, and Asn336A and new H-bonds with Lys22A, Arg226A, Val227A, Ser230A, Asn236A, and Leu370A. However, for GLAMut4 conjugate (Figure 5s and Supplementary Information Table S5s) increased H-bonds (nineteen) and ten hydrophobic interactions were observed, as was a \(\pi\)-stacking interaction with Tyr334. New H-bonds included those with Tyr214A, Lys222A, Leu254A, Ala256A, Cys275A, Glu282A, Ser323A, and Gly335A, indicating overall higher interactions. RMAMut4 (Figure 5t and Supplementary Information Table S5t) showed relatively less (seven) hydrophobic interactions, including new ones with Lys257A, Val332A, and Ile689B. Thirteen H-bonds were still formed, including new ones with Leu254A, Ala256A, Glu282A, Thr285A, His457A, and Arg692B. A \(\pi\)-stacking interaction with Tyr334A, a \(\pi\)-cation interaction with His457A, and two salt bridges with Arg692B were also formed.