{'fraction_non_alphanumeric': 0.020860495436766623, 'fraction_numerical': 0.011299435028248588, 'mean_word_length': 5.238482384823849, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Molecular mechanism of capsid disassembly in hepatitis B virus

Significance Hepatitis B virus (HBV) is a DNA virus that is 100 times more infectious than HIV. Despite the availability of a vaccine, the chronic infection rate of this virus is still over 250 million people globally. HBV chronic infection, for which no cure is currently available, can lead to liver cancer. Therefore, there is an unmet need to investigate the infection cycle of the virus. One of the most crucial steps in the virus-replication cycle is the release of its genetic material to the nucleus. During this step, the viral capsid enclosing the genetic material disassembles. However, its mechanism is unknown. Here, we utilize molecular simulations to shed light on the events leading to the capsid disassembly with atomistic detail. The disassembly of a viral capsid leading to the release of its genetic material into the host cell is a fundamental step in viral infection. In hepatitis B virus (HBV), 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 subjected to a uniform mechanical stress protocol, we monitor the capsid-disassembly process and analyze the process down to the level of individual amino acids in 20 independent simulation replicas. The strain of an isotropic external force, combined with structural fluctuations, causes structurally heterogeneous cracks to appear in the HBV capsid. Analysis of the monomer–monomer interfaces reveals that, in contrast to the expectation from purely mechanical considerations, the cracks mainly occur within hexameric sites, whereas pentameric sites remain largely intact. Only a small subset of the capsid protein monomers, different in each simulation, are engaged in each instance of disassembly. We identify specific residues whose interactions are most readily lost during disassembly; R127, I139, Y132, N136, A137, and V149 are among the hot spots at the interfaces between dimers that lie within hexamers, leading to disassembly. The majority of these hot-spot residues are conserved by evolution, hinting to their importance for disassembly by avoiding overstabilization of capsids.