Alternate conformational states of the HIV-1 capsid protein: Atomistic structures and dynamics of interconversion.

The HIV-1 capsid protein assembles into a conical shell that encases the viral RNA genome. The capsid protein is a two-domain protein, with the C-terminal domain (CTD) forming a dimer. Depending on being in a solution environment or the crystalline state, different dimer arrangements have been observed for the full capsid protein, as well as a truncated construct consisting of only the CTD. To characterize the structures and dynamics of these alternate quaternary arrangements, we carried out atomistic simulations using the weighted ensemble enhanced sampling strategy. Our simulations generated continuous pathways for interconversion between the two states with rate constants that agree with those measured by 19F NMR exchange spectroscopy. Our results demonstrate the advantages of pairing atomistic simulations with 19F NMR and have implications for the structural polymorphism of the HIV-1 viral capsid assembly process.