Simulated self-assembly of the HIV-1 capsid: protein shape and native contacts are sufficient for two-dimensional lattice formation

We report Monte Carlo simulations of the initial stages of self-assembly of the HIV-1 capsid protein (CA), using a coarse-grained representation that mimics the CA backbone structure and intermolecular contacts observed experimentally. A simple representation of N-terminal domain/N-terminal domain and N-terminal domain/C-terminal domain interactions, coupled with the correct protein shape, is sufficient to drive formation of an ordered lattice with the correct hexagonal symmetry in two dimensions. We derive an approximate concentration/temperature phase diagram for lattice formation, and we investigate the pathway by which the lattice develops from initially separated CA dimers. Within this model, lattice formation occurs in two stages: 1), condensation of CA dimers into disordered clusters; and 2), nucleation of the lattice by the appearance of one hexamer unit within a cluster. Trimers of CA dimers are important early intermediates, and pentamers are metastable within clusters. Introduction of a preformed hexamer at the beginning of a Monte Carlo run does not directly seed lattice formation, but does facilitate the formation of large clusters. We discuss possible connections between these simulations and experimental observations concerning CA assembly within HIV-1 and in vitro.