Objective: To analyze the physicochemical properties of HIV-1 gp120, and investigate the interaction with the human CD4 receptor, providing structural insights for antibody and vaccine design. Methods: The PDB files of gp120 and CD4 were obtained from the Protein Data Bank and AlphaFold Protein Structure Database. The Expasy-ProtParam tool was utilized to analyze the physicochemical properties of HIV-1 gp120. ClusPro 2.0 was employed to perform protein-protein docking between gp120 and CD4, and PyMOL was used to visualize binding sites and analyze interacting residues. Results: Physicochemical analysis revealed that the gp120 core (molecular weight 39,168.53 Da) has a theoretical isoelectric point of 6.84 and an instability index of 39.09, classifying it as a stable protein. The docking models identified key amino acid residues involved in the gp120-CD4 interaction, including GLN-39, ASP-35, THR-28, HIS-18, CYS-31, and GLU-44, primarily driven by hydrogen bonds and electrostatic interactions. Conclusion: These results demonstrate that the uncleaved gp120 core maintains a native-like stable structure with specific hydrophilic and charged interaction sites for CD4. This structural stability and the identified binding interfaces support the potential of gp120 as a candidate for antibody-mediated immune response targeting and vaccine development.