Abstract: Hepatitis B virus infection is a global health problem that seriously threatens human health. It is related to the development of liver cirrhosis and hepatocellular carcinoma, and can cause different types of liver damage. Unfortunately, there has been no accomplished functional cure in chronic hepatitis B (CHB) to date. After in-depth study of the interactions between different HBV proteins and their ligands, it was found that the interaction between specific ligands and key amino acids actually acts as a "switch" for the anti-HBV potency of a compound. Based on this finding, molecular docking technology was applied to analyze the binding mode between the protein and the ligand. By comparing and analyzing the similarities between the small molecules of different ligands, the potential pharmacophores were successfully determined, and the possible interactions between amino acids and these compounds were further explored. These studies not only deepen our understanding of the diversity of shape and structure of HBV capsid assembly modulator (CAM), but also enable us to obtain a new understanding of pharmacophore similarity, which provides some insight for rational design of antiviral drugs.