Background. Bulevirtide (BLV) is the only drug approved by the European Medicines Agency and the Food and Drug Administration for the treatment of chronic hepatitis D, a severe liver disease caused by hepatitis D virus (HDV) infection in individuals infected with hepatitis B virus (HBV). BLV is an entry inhibitor that competitively binds to the Na+-taurocholate cotransporting polypeptide (NTCP), the cellular receptor used by both HDV and HBV for hepatocyte entry [1—2]. Methods. Molecular dynamics simulations of NTCP with and without BLV were performed using the 8RQF structure [2] in GROMACS 2023.3 [3] with the CHARMM36m force field [4] for 300 ns, followed by comparative structural and dynamic analyses. Results. Because BLV is an N-myristoylated lipopeptide, the topology parameters for the N-terminal N-tetradecanoylglycine residue compatible with the CHARMM36m force field were developed, enabling simulation of the complete BLV-NTCP complex. BLV binding did not substantially alter NTCP compactness, as indicated by similar radius of gyration and solvent-accessible surface area values in the bound and unbound states. However, the principal component and free energy landscape analyses revealed distinct predominant conformational states of free and BLV-bound NTCP. Throughout the simulation, BLV formed a mean of 13.7 ± 3.0 hydrogen bonds with NTCP, while the mean binding free energy of the BLV-NTCP complex was −186.9 ± 24.5 kcal/mol, indicating a highly stable protein-ligand complex. Conclusions. These findings provide molecular-level support for the mechanism underlying BLV-mediated inhibition of HDV and HBV entry and highlight NTCP as a promising target for the development of additional competitive entry inhibitors.