## 3 Results
### Binding Affinity of Ginsenosides with ADGRG3  
In the virtual screening of ginsenosides against ADGRG3, identified five top candidates ginsenosides Rg3, Rk3, F5, Rg7, and F1 based on their strong binding affinities and stable interactions within the ADGRG3 binding pocket, as shown in Table 1 and illustrated in Figure 6 and Supplementary Figure S5. Ginsenoside Rg3 had the highest binding affinity (\(-\)10.7 kcal/mol), with five hydrogen bonds involving key residues such as TYR 406 and ARG 409, along with additional hydrophobic contacts. Rk3 and F5 followed closely with binding energies of \(-\)10.6 and \(-\)10.5 kcal/mol, respectively. Rk3 formed one hydrogen bond with TYR 406 and several hydrophobic contacts, whereas F5 formed four hydrogen bonds and additional stabilizing interactions, which was comparable to HCY's binding pattern.  
Rg7 and F1 also showed strong binding, with binding energies of \(-\)10.4 and \(-\)10.3 kcal/mol, respectively. Both engaged key residues through hydrogen bonding, with Rg7 particularly aligning with ALA 493 and ASN 510, which was similar to the control ligands. Compared to the top two controls dexamethasone and HCY which showed binding energies of \(-\)10.3 and \(-\)10.4 kcal/mol, respectively, the selected ginsenosides displayed comparable or stronger binding and stable interactions, supporting their potential as ADGRG3-targeting agents. These top candidates demonstrate promising binding stability within the ADGRG3 site, warranting further MDS to assess their therapeutic potential in cancer.  
\begin{table}
\begin{tabular}{p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt}} \hline \hline
**Protein** & **Compound** & \begin{tabular}{c} **Binding** \\ **Energy** \\ **(kcal/mol)** \\ \end{tabular} & \begin{tabular}{c} **Hydrogen Bond** \\ **Interactions** \\ \end{tabular} & \begin{tabular}{c} **Other Interactions** \\ **Bonds** \\ \end{tabular} \\ \hline \multirow{8}{*}{**ADGRG3**} & Ginsenoside Rg3 & \(-\)10.7 & \begin{tabular}{c} TYR 406, ARG 409, \\ TYR 432, **ALA 493**, \\ PHE 495 \\ \end{tabular} & HIS 436, **TRP 490** & 5 \\ \cline{2-5}  & Ginsenoside Rk3 & \(-\)10.6 & \begin{tabular}{c} TYR 406 \\ **TRP 490, ALA 493**, **ASN 510** \\ \end{tabular} & \(1\) \\ \cline{2-5}  & Ginsenoside F5 & \(-\)10.5 & \begin{tabular}{c} SER 272, CYS 276, \\ **ALA 493, ASN 510** \\ \end{tabular} & LEU 349, TYR 406, \\ \cline{2-5}  & Ginsenoside Rg7 & \(-\)10.4 & \begin{tabular}{c} TYR 406, ARG 409, \\ **ALA 493, ASN 510** \\ \end{tabular} & LEU 349, ILE 494 & 4 \\ \cline{2-5}  & Ginsenoside F1 & \(-\)10.3 & \
\begin{tabular}{c} GLY 357, TYR 438, \\ THR 442 \\ \end{tabular} & VAL 385, LEU 389, \\ \cline{2-5}  & Dexamethasone & \(-\)10.3 &
\begin{tabular}{c} **PHE 506, ASN 510** \\ \end{tabular} & **ALA 493** & 2 \\ \cline{2-5}  & HCY (hydrocortisone) & \(-\)10.4 & **ASN 510** & LEU 319, PHE 345, \\ \cline{2-5}  & HCY (hydrocortisone) & \(-\)10.4 & **ASN 510** & **TRP 490, ALA 493,** \\ \cline{2-5}  & & & & \(\;\;\) PHE 506 \\ \hline \hline \end{tabular}  
* The bold indicates the key amino acid residues engage in bonding as similar to control ligands.  
\end{table}
Table 1: Interactions of the top five ginsenosides with the amino acid residue of ADGRG3.