Structural basis for nuclear import of hepatitis B virus (HBV) nucleocapsid core.

Nuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in the nucleus. The ~360-angstrom HBV capsid translocates to the nuclear pore complex (NPC) as an intact particle, hijacking human importins in a reaction stimulated by host kinases. This paper describes the mechanisms of HBV capsid recognition by importins. We found that importin α1 binds a nuclear localization signal (NLS) at the far end of the HBV coat protein Cp183 carboxyl-terminal domain (CTD). This NLS is exposed to the capsid surface through a pore at the icosahedral quasi-sixfold vertex. Phosphorylation at serine-155, serine-162, and serine-170 promotes CTD compaction but does not affect the affinity for importin α1. The binding of 30 importin α1/ß1 augments HBV capsid diameter to ~620 angstroms, close to the maximum size trafficable through the NPC. We propose that phosphorylation favors CTD externalization and prompts its compaction at the capsid surface, exposing the NLS to importins.

AMBERff at Scale: Multimillion-Atom Simulations with AMBER Force Fields in NAMD.

All-atom molecular dynamics (MD) simulations are an essential structural biology technique with increasing application to multimillion-atom systems, including viruses and cellular machinery. Classical MD simulations rely on parameter sets, such as the AMBER family of force fields (AMBERff), to accurately describe molecular motion. Here, we present an implementation of AMBERff for use in NAMD that overcomes previous limitations to enable high-performance, massively parallel simulations encompassing up to two billion atoms. Single-point potential energy comparisons and case studies on model systems demonstrate that the implementation produces results that are as accurate as running AMBERff in its native engine.