Molecular Docking and Dynamic Simulation Studies of Benzoylated Emodin into HBV Core Protein

Objectives: The hepatitis B virus (HBV) core protein was chosen as receptor target for a new, selective and effective due to resistance of current hepatitis B drugs against reverse transcriptase. It forms the capsid of viral particles and essential for viral genome DNA replication and maturation. Emodin was known showing inhibitory effect on HBV replication weakness, but persistent both in vitro and in vivo so still need modification. In this study, emodin derivatives were conducted as an inhibitor candidate of capsid assembly by disruption formation dimer-dimer HBV core protein using molecular docking and dynamic simulation. Materials and Methods: Structure-based virtual docking approach was used to design of benzoylated emodin derivatives into HBV core protein as receptor using Molegro Virtual Docker 6.0 program. The stability of interacting residues of proteins with compounds was identified via molecular dynamics and free binding energy calculations using Amber 12. Results: The ligand binding site in an HBV core protein was an interfacial hydrophobic pocket and placed at the dimer-dimer of the core protein interface. Interactions between emodin and derivatives indicated by hydrogen bonding and steric interaction between the ligand with the amino acid residues in the HBV core protein. It is predicted that viral replication would inhibit due to a change in orientation of capsid assembly by core proteins. The benzoylated emodin derivatives showed promising inhibitory profiles better than emodin which were indicated by their binding scores were more negative. Conclusion: This study provides a basis for further chemical design for more effective derivatives of emodin derivatives.