## 3 Results
### Molecular Interaction Dynamics of Ginsenosides with ADGRG3  
In this study, MDSs were conducted to examine the stability, flexibility, compactness, and interaction dynamics of ADGRG3 in complex with several ginsenosides (Rg3, RK3, F5, Rg7, and F1) and two valid control ligands--dexamethasone and hydrocortisone (HCY). Key structural parameters, including the RMSD, root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding patterns, were analyzed. The RMSD analysis (Figure 8A) provided insights into the overall stability of the ADGRG3-ligand complexes throughout the simulation period. The RMSD profiles of ADGRG3 complexed with the ginsenosides and controls revealed varying degrees of stability. The Rg3 and RK3 complexes showed relatively stable RMSD values over the simulation time, indicating strong and consistent binding to ADGRG3. In contrast, F5 and F1 displayed minor fluctuations, suggesting moderate flexibility in binding. The control ligands, dexamethasone and HCY, showed comparable RMSD patterns, with HCY presenting slightly higher RMSD values, indicating marginally lower stability compared to dexamethasone-sone. The RMSF analysis (Figure 8B) highlighted the flexibility of individual residues in ADGRG3 when complexed with each ligand. Both Rg3 and RK3 complexes showed lower RMSF values across most residues, indicating limited fluctuations and a generally stable conformation. In contrast, F5 and Rg7 complexes exhibited higher fluctuations in specific regions, suggesting areas of increased flexibility in the binding site. The control ligand HCY showed moderate fluctuations, whereas dexamethasone demonstrated relatively stable binding with limited residue flexibility, indicating that both control ligands engage the receptor with distinct but stable binding patterns. The radius of gyration (Rg) analysis (Figure 9A) reflected the compactness of the ADGRG3-ligand complexes over the simulation period. Ginsenosides Rg3 and F5 showed lower Rg values, suggesting that ADGRG3 maintains a compact structure in these com  
Figure 8: (**A**) RMSD values of ginsenoside Rg3, ginsenoside RK3, ginsenoside F5, ginsenoside Rg7, ginsenoside F1, and controls (dexamethasone and HCY) in complex with ADGRG3. (**B**) RMSF values of ginsenoside Rg3, ginsenoside R3, ginsenoside F5, ginsenoside Rg7, ginsenoside F1, and controls (dexamethasone and HCY) in complex with ADGRG3. plexes. The higher Rg values observed with Rg7 and F1 indicated a slightly expanded structure, possibly due to the conformational adaptations required for optimal binding. Both dexamethasone and HCV displayed consistent Rg values, indicating stable complex compactness, with HCY showing marginally higher Rg values than dexamethasone. The hydrogen bonding patterns (Figure 9B) illustrated the binding strength and stability of the ADGRG3-ligand interactions. Ginsenoside Rg3 and Rk3 formed a higher average number of hydrogen bonds with ADGRG3, supporting their stable binding profiles observed in the RMSD and Rg analyses. In comparison, the RG7 and F5 complexes exhibited fewer hydrogen bonds, suggesting weaker interactions. Dexamethasone and HCY displayed moderate hydrogen bonding stability, with HCY forming slightly fewer bonds than dexamethasone-sone, aligning with its somewhat higher RMSD and Rg values. Overall, the MDS analysis revealed that Rg3 and Rk3 exhibit the most stable binding profiles with ADGRG3, as evidenced by their low RMSD values, stable RMSF values, compact Rg, and strong hydrogen bonding interactions. These findings suggest that Rg3 and Rk3 may be promising candidates for targeting ADGRG3 after the validation of this outcome in preclinical cell-based assays. Further, binding free energy calculations for the seven complexes were conducted using the MM-PBSA method, leveraging the GROMACS software and MDS (MD) trajectories. The results obtained indicated that the binding energies were within a favorable range, suggesting robust interactions.