Hepatitis B virus core protein (HBV Cp) is closely involved in the viral assembly, nuclear functions, compartment for reverse transcription, and intra-cellular trafficking. Therefore, modulation of HBV Cp assembly is a promising method to control HBV infection in both preclinical and clinical studies. In this paper, two ligands of HAP18 and AT-130, as representations of heteroaryldihydropyrimidines and phenylpropenamides, have been chosen. Their Binding modes and conformations docking with the HBV Cp have been simulated by a Monte Carlo method. Strong polar contact in HAP18-bound and relatively weak interaction dominated by the Lennard-Jones potential in AT130-bound have been observed, respectively. Although different binding modes result in different assembly behaviors of HBV core protein, both of them strongly influence the quaternary structure of the Cp assembly, changing the spatial relationship between dimers, and inducing noninfective Cp misassembly. The simulation is expected to be helpful to get some insight into the antiviral mechanism of HBV Cp assembly modulation.