## 5 Conclusions  
This study predicted that ADGRG3/GPR97 could be a target in cancer and immune modulation, which is supported by the results of integrative computational analyses. Virtual screening identified five ginseng-Rg3, RK3, F5, Rg7, and F1--as probable ADGRG3-targeting ligands, with Rg3 showing the highest binding affinity and stability in MDS and free binding energy calculations. The favorable in silico ADMET profiles further highlighted these ginseng as safe, natural alternatives to synthetic drugs. Pathway and protein-protein interaction analyses linked ADGRG3 to critical GPCR and immune pathways, such as neutrophil degranulation and Ca\({}^{2+}\) signaling, emphasizing its role in tumor microenvironment modulation. The gene expression analysis of 506 AML samples revealed high ADGRG3 expression in 70-80% of cases and co-expression with genes such as GNB1, GNG2, and CXCL8, further supporting its role in AML progression. These findings provide a robust basis for ADGRG3-targeted therapies, highlighting ginsengosides as possible modulators, particularly in elevated ADGRG3 expression. Further in vitro and in vivo preclinical and clinical studies are warranted to validate ginseng regulations in ADGRG3, as determined by these computational predictions. **Supplementary Materials:** The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/app15084332/s1](https://www.mdpi.com/article/10.3390/app15084332/s1)]([https://www.mdpi.com/article/10.3390/app15084332/s1](https://www.mdpi.com/article/10.3390/app15084332/s1)), Figure S1: The genetic alterations of ADGRG3 and associations with mRNA expression. (A) Total genetic alterations of ADGRG3 genes based on cbioportal website. (B) Bubble map indicated the relationship between ADGRG3 mRNA expression and CNV. Red dots indicate that gene CNV levels were positively associated with mRNA expression, blue dots indicate the negative association; Figure S2: ADGRG3 mutation in pan-cancer based on cbioportal website. (A) Oncoprinter of ADGRG3 in different cancer types. (B) Amino acid mutation of ADGRG3. The important mutation sites that predicted as damaging in both GPS and 7 tm_2 algorithms in the functional and structural importance of the protein sequence position; Figure S3: The effect of GPR97 expression level on (A) LAML, (B) CHOL, (C) HNSC, (D) PAAD patient survival; Figure S4: TME analysis for ADGRG3 gene in (A) CHOL, (B) PAAD and (C) HNSC cancers. The immune infiltration correlation provide insights into GPR97's potential impact on immune microenvironments and patient survival; Figure S5: 2D interaction diagram of ADGRG3 with (A) Ginsenoside Rg3, (B) Ginsenoside Rx3, (C) Ginsenoside F5, (D) Ginsenoside Rg7, (E) Ginsenoside F1, (F) Dexamethasone, and (G) HCY; Figure S6: KEGG Enrichment Analysis of the top 20 genes in the PPI network of ADGRG3; Table S1: Grid box coordinates and size parameters used for molecular docking; Table S2: Active site prediction for ADGRG3 using DoGSiteSco; Table S3: Parameters evaluated for drug-likeness of ginsengides and the control drugs; Table S4: Parameters evaluated for absorption of ginsengides and the control drugs; Table S5: Parameters evaluated for distribution of ginsengides and the control drugs; Table S6: Parameters evaluated for metabolism of ginsengides and the control drugs; Table S7: Parameters evaluated for excretion of ginsengides and the control drugs; Table S8: Parameters evaluated for toxicity of ginsengides and the control drugs. File SI: List of ginsengides used, docking scores, PPI genes, GO and KEGG analysis. **Funding:** This Research was supported by Seokyeong University in 2023. **Institutional Review Board Statement:** Not applicable. **Informed Consent Statement:** Not applicable. **Data Availability Statement:** All of the data generated or analyzed during this study are included in the article and Supplementary Materials. **Acknowledgments:** This Research was supported by Seokyeong University in 2023. I thank [PERSON] and [PERSON] for their valuable support and guidance.