All-atom molecular dynamics study of hepatitis B virus containing pregenome RNA in solution

Kazushi Fujimoto, Youhei Yamaguchi, Ryo Urano, Wataru Shinoda, Tetsuya Ishikawa, Katsumi Omagari, Yasuhito Tanaka, Atsushi Nakagawa, Susumu Okazaki

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Immature hepatitis B virus (HBV) captures nucleotides in its capsid for reverse transcription. The nucleotides and nucleotide analog drugs, which are triphosphorylated and negatively charged in the cell, approach the capsid via diffusion and are absorbed into it. In this study, we performed a long-time molecular dynamics calculation of the entire HBV capsid containing pregenome RNA to investigate the interactions between the capsid and negatively charged substances. Electric field analysis demonstrated that negatively charged substances can approach the HBV capsid by thermal motion, avoiding spikes. The substances then migrate all over the floor of the HBV capsid. Finally, they find pores through which they can pass through the HBV capsid shell. Free energy profiles were calculated along these pores for small ions to understand their permeability through the pores. Anions (Cl) showed higher free energy barriers than cations (Na+ and K+) through all pores, and the permeation rate of Cl was eight times slower than that of K+ or Na+. Furthermore, the ions were more stable in the capsid than in the bulk water. Thus, the HBV capsid exerts ion selectivity for uptake and provides an environment for ions, such as nucleotides and nucleotide analog drugs, to be stabilized within the capsid.

Original languageEnglish
Article number145101
JournalJournal of Chemical Physics
Issue number14
Publication statusPublished - Oct 14 2021
Externally publishedYes

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry


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