## 3 Results and Discussion
### Binding Interaction Analysis with PLIP
#### 3.5.2 Interactions with PPAR-\(\alpha\)
As seen in Figure 5b and Supplementary information Table S5b, eight hydrogen bonds and nine hydrophobic interactions were observed for CSAPeP, while a \(\pi\)-stacking interaction occurred with Tyr334A of PPAR-\(\alpha\). Hydrogen bonds were still observed with Thr279A and Tyr334A, while all others were seen with new residues, including Lys224A, Glu282A, and Asn336A. All hydrophobic interactions, except for two with Tyr334A, were formed with new residues, including Val255A, Val281A, Glu282A, Thr285A, Glu286A, and Glu289A. The GLAPep conjugate displayed fourteen hydrogen bonds and thirteen hydrophobic interactions, as seen in Figure 5c and Supplementary Information Table S5c. New hydro  
Figure 4: PLIP results for each of the peptides bound to PPAR\(\alpha\) receptor. (**a**) Original peptide; (**b**) Mut1 (**c**) Mut2 (**d**) Mut3 (**e**) Mut4. gen bonds included those with Asn219A, Lys224A, Ser334A, Asn236A, Ile272A, Cys275A, Glu282A, and Asn336A, while new hydrophobic interactions were observed with Asn219A, Lys224A, Ile228A, Asn236A, Leu254A, Val255A, Glu282A, and Ile339A. Conjugation with rosmarinate (RMAPep) improved the binding affinity of Pep for PPAR-\(\alpha\). As shown in Figure 5d and Supplementary Information Table S5d, seventeen hydrophobic interactions and fourteen hydrogen bonds were observed. Hydrogen bonds observed included those with Asn219A, Met220A, Cys275A, Glu282A, Thr285A, Glu286A, and Arg692B, while new hydrophobic interactions included those with Leu254A, Val255A, Ile317A, Phe318A, Met320A, Val324A, and Leu693B. Additionally, two \(\pi\)-stacking interactions were formed with Tyr334. The conjugate CGAMut1 (Figure 5e and Supplementary Information Table S5e) showed eleven H-bonds and fourteen hydrophobic interactions. New H-bonds were observed with  
Figure 5: PLIP results for polyphenol peptide conjugates bound to PPAR-\(\alpha\) receptor. Pep conjugated with (**a**) chlorogeneate; (**b**) carnosate (**c**) gallate (**d**) rosmarinate. Mut1-conjugated with (**e**) chlorogeneate; (**f**) carnosate; (**g**) gallate; (**h**) rosmarinate. Mut2-conjugated with (**i**) chlorogeneate (**j**) carnosate; (**k**) gallate; (**l**) rosmarinate. Mut 3-conjugated with (**m**) chlorogeneate; (**n**) carnosate; (**o**) gallate; (**p**) rosmarinate; Mut4-conjugated with (**q**) chlorogeneate; (**r**) with carnosate; (**s**) gallate; (**t**) rosmarinate. Asn219A, Cys275A, Glu282A, and Glu289A, while new hydrophobic interactions occurred with Leu254A, Val255A, Leu258A, Glu282A, Thr285A, Glu286A, and Glu289A. As shown in Figure 5f and Supplementary Information Table S5f, carnosate-Mut1 (CSAMut1) conjugate displayed eight hydrophobic interactions and nine H-bonds, while the \(\pi\)-stacking was not maintained. Several hydrophobic interactions seen for Mut1 alone were eliminated, while new ones formed. New H-bonds were also observed with Glu282A, Glu289A, Arg692B, and Glu696B. A \(\pi\)-stacking interaction was observed with Tyr334A. The GLAMut1 conjugate exhibited thirteen hydrophobic interactions and ten hydrogen bonds as shown in Figure 5g and Supplementary Information Table S5g. New hydrophobic interactions were observed with Leu247A, Glu251A, Val255A, and Val281A. A new hydrogen bond was observed with Leu331A. A salt bridge also occurred with His457A. The RMAMut1 (Figure 5h and Supplementary information Table S5h), formed fifteen H-bonds and twenty hydrophobic interactions. New H-bonds were seen with Ser280A, Glu282A, Met320A, His440A, and Arg692B. New hydrophobic interactions occurred with Leu247A, Val255A, Ile272A, Thr285A, Phe318A, Ile339A, His457A, and Leu693B. \(\pi\)-stacking was observed between Tyr334 and a \(\pi\)-cation interaction was shown between His274 of PPAR-\(\alpha\) and Tyr6 of RMAMut1. The CGAMut2 conjugate (Figure 5i and Supplementary information Table S5i), formed eleven hydrophobic interactions, with new ones occurring with Leu254A, Val281A, Thr285A, Glu286A, Glu289A, and Leu459A.