## 3 Results and Discussion
### Binding Interaction Analysis with PLIP
#### 3.5.3 Interactions with EGFR
New hydrophobic interactions included those with Val726A, Thr854A, Trp880A, and Pro914A, while new hydrogen bonds occurred with Ser720A and Thr854. RMAMut 1 in comparison displayed thirteen hydrophobic interactions and ten hydrogen bonds, in addition to one \(\pi\)-cation interaction and one salt bridge with Lys879A as seen in Figure 7h and Supplementary Information Table S7h. Compared to Mut1 alone, new hydrophobic interactions occurred with Gly721A, Ala722A, Phe723A, Val726A, Leu799A, Thr854A, Lys879A, and Ala920A, while new hydrogen bonds were observed with Leu718A, Ser720A, Gly721A, Cys797A, Lys879A, Gly911A, Lys913A, and Ala920A. The CGAMut2 conjugate showed only seven hydrophobic interactions, nine hydrogen bonds, and one salt bridge, as shown in Figure 7i and Supplementary Information Table S7i. Figure 7: PLIP results for polyphenol peptide conjugates bound to EGFR (**a**) CGAPep (**b**) CSAPep (**c**) GLAPep (**d**) RMAPep (**e**) CGAMut1; (**f**) CSAMut1; (**g**) GLAMut1; (**h**) RAMMut1; (**i**) CGAMut2 (j) CSAMut2; (**k**) GLAMut2; (**l**) RAMut2; (**m**) CGAMut3; (**n**) CSAMut3; (**o**) GLAMut3; (**p**) RMAMut3; (**q**) CGAMut4; (**r**) CSAMut4; (**s**) GLAMut4; (**t**) RAMMut4. Compared to Mut2 alone, new hydrophobic interactions were formed with Val717A and Asp800A, while new H-bonds were formed with Val717A, Ala722A, Arg841A, and Lys913A. CSAMut2 comparatively displayed ten hydrophobic interactions and four hydrogen bonds, in addition to one salt bridge with Arg841A, as seen in Figure 7j and Supplementary Information Table S7j. New hydrophobic interactions were seen with Ser720A, Ala722A, Leu799A, Asp800A, and Trp880A. The GLAMut2 conjugate, on the other hand, showed eleven hydrophobic interactions and six hydrogen bonds, as shown in Figure 7k and Supplementary Information Table S7k. Several new hydrophobic interactions were seen, while new H-bonding occurred with Tyr801A, Lys846A, Gln849A, and Met987A. The large change in interactions observed following conjugation of Mut2 with gallate indicates a change of position of the conjugate within the EGFR binding site. RMAMut2 showed only six hydrophobic interactions and eight hydrogen bonds, in addition to two salt bridges with Arg803A and Lys879A, shown in Figure 7l and Supplementary Information Table S7l. Compared to Mut2 alone, new hydrophobic interactions were observed with Ser720A, Ala722A, Arg803A, and Trp880A, while new H-bonds formed with Ala722A, Asp800A, Arg841A, Val876A, Lys879A, Gly917A, and Ala920A. CGAMut3 exhibited seven hydrophobic interactions and ten hydrogen bonds were observed, as well as a salt bridge with Arg841A, indicated in Figure 7m and Supplementary Information Table S7m. Compared to Mut3 alone, new hydrophobic interactions were observed with Leu718A, Gly719A, Ser720A, Leu799A, Asp800A, and Asn996A. New H-bonds were seen with Ser710A, Ala722A, Lys745A, Asp800A, and Asn996A. As seen in for CSAMut3 (Figure 7n and Supplementary Information Table S7n), ten hydrophobic interactions, eight hydrogen bonds, and one \(\pi\)-stacking interaction were seen. New hydrophobic interactions included those with Ala722A, Val726A, Leu844A, Thr854A, Val876A, Ile878A, and Trp880A, while new H-bonds included those with Lys745A, Arg841A, Val876A, Lys879A, Ile918A, and Ala920A. The GLAMut3 conjugate, as indicated in Figure 7o and Supplementary Information Table S7o, showed nine hydrophobic interactions and eight hydrogen bonds. New hydrophobic interactions included those with Leu718A, Val726A, Asp800A, Leu844A, and Trp880A, while new hydrogen bonds were seen with Leu718A, Asp800A, and Arg841A. RMAMut3 (Figure 7p and Supplementary Information Table S7p) showed seven hydrophobic interactions, including new ones with Leu718A, Gly719A, Leu799A, Asp800A, Lys879A, and Trp880A. Eight H-bonds, including new ones with Val717A, Gly719A, Ser720A, and Val876A, were formed. CGAMut4, as shown in Figure 7q and Supplementary Information Table S7q, seven hydrophobic interactions, thirteen hydrogen bonds. One salt bridge with Lys745A was observed.