Hepatitis B viral capsid disassembly and genome synthesis: from the atomic level to the whole cell

Abstract

The disassembly of hepatitis B viral capsid, which leads to the release of its genetic material into the host cell nucleus, is a fundamental step in the infection cycle, speculated to occur at the nuclear pore complexes (NPCs) within the nuclear envelope. The capsid consists of identical protein monomers that dimerize and then arrange themselves into pentamers or hexamers on the capsid surface. By applying atomistic molecular dynamics simulation to an entire solvated HBV capsid, totaling ∼6 million atoms, and engineering a mechanical stress mimicking the impact of the nuclear pores, we monitor the capsid disassembly and analyze the process down to the level of individual amino acids in 20 independent simulation replicas.