## 5 Docking Analysis of AMPK with Flavonoids
The interaction features hydrogen bonds and pi-sigma, pi-alkyl, and pi-sulfur interactions, suggesting a robust binding configuration that may contribute to AMPK activation. **(B)** Dihydromyricetin exhibited a docking score of \(-7.3\), signifying a significant, though slightly lower, binding affinity to the \(\alpha\)1 subunit of AMPK. The primary contact residues include LEU22, GLY23, VAL30, ALA43, ILE77, MET93, GLU94, TYR95, VAL96, GLY99, GLU100, ASP103, LEU146, ALA156, and ASP157. The interaction primarily involved hydrogen bonds and pi-alkyl interactions, indicating stable binding that could also facilitate AMPK activation. In contrast, 7-O-MA (Figure 4B) demonstrated a more robust interaction with a docking score of \(-6.8\). This flavonoid also targeted the \(\alpha 1\) subunit, interacting with key residues like LEU22, GLY23, VAL30, ALA43, LYS45, ILE77, and MET93, among others. The binding involved a stable network of hydrogen bonds and pi-alkyl interactions, indicating that 7-O-MA could be a stronger candidate for AMPK activation than bavachin. Figure 4: Molecular docking analysis of bavachin and 7-O-methylaromadendrin with AMPK’s \(\alpha 1\), \(\beta 1\), and \(\gamma 1\) subunits (PDB ID 4 QFG). This figure presents the molecular docking results for AMPK (\(\alpha 1\), \(\beta 1\), and \(\gamma 1\) subunits; PDB ID: 4 QFG) with the flavonoids bavachin (**A**) and 7-O-methylaromadendrin (7-O-MA) (**B**). (**A**) Bavachin showed a docking score of \(-4.4\), indicating moderate binding affinity with the \(\alpha 1\) subunit. The key contact residues involved in this interaction include LEU22, VAL30, ALA43, LYS45, GLU64, LEU68, ILE77, MET93, GLU94, and others, involving hydrogen bonds and pi-alkyl and pi-sulfur interactions. (**B**) 7-O-MA demonstrated a stronger binding affinity with a docking score of \(-6.8\), also targeting the \(\alpha 1\) subunit. The interaction was characterized by several contact residues, such as LEU22, GLY23, VAL30, ALA43, LYS45, ILE77, MET93, GLU94, and others, forming a stable interaction network primarily through hydrogen bonds and pi-alkyl interactions. Derrone (Figure 5A) showed a strong docking score of \(-7.4\), with significant interactions involving the \(\alpha\)1 subunit of AMPK. The binding included residues such as LEU22, GLY23, VAL24, THR26, VAL30, and others, suggesting that derrone could effectively stabilize and activate the AMPK complex through a combination of hydrogen bonding and non-covalent interactions. Figure 5: Molecular docking analysis of derrone and alipunimsoflavone with AMPK’s \(\alpha\)1, \(\beta\)1, and \(\gamma\)1 subunits (PDB ID 4 QFG). This figure presents the results of molecular docking studies involving the interaction of AMPK (\(\alpha\)1, \(\beta\)1, and \(\gamma\)1 subunits; PDB ID 4 QFG) with the flavonoids derrone (**A**) and alipunimsoflavone (**B**). (**A**) Derrone exhibited a docking score of \(-7.4\), indicating strong binding affinity to the \(\alpha\)1 subunit of AMPK. The key residues involved in this interaction include LEU22, GLY23, VAL24, THR26, VAL30, and several others, forming a stable network of hydrogen bonds and non-covalent interactions. (**B**) Alipunimsoflavone demonstrated a docking score of \(-3.4\), suggesting a weaker interaction with the \(\alpha\)1 subunit of AMPK. The binding interaction of Alipunimsoflavone with AMPK primarily involved hydrogen bonds with VAL96, GLY25, GLY99, and GLU143, an unfavorable acceptor-acceptor interaction with GLU100, a pi-sigma interaction with LEU146, and pi-alkyl interactions with LEU22, TYR95, and VAL96. Alpinumiosflavone (Figure 5B), however, displayed a lower docking score of \(-3.4\), indicating a weaker binding affinity to the \(\alpha 1\) subunit of AMPK. The interaction profile involved residues like LEU22, GLY23, VAL24, THR26, and GLU100, suggesting that while alpinumiosflavone might interact with AMPK, its potential to modulate AMPK activity is likely less pronounced compared to derrone.