Self-Assembly of Elastic Capsomeres into a Virus Capsid: Experimentally-Informed Molecular Dynamics Simulations

In many viruses, capsomeres self-assemble spontaneously to form symmetric icosahedral capsids. The nature of this self-assembly and the formation of intermediate structures is important for antiviral drug development as well as the design of nanoparticle-based drug-delivery carriers. However, this self-assembly process is not completely understood in part due to vastly different timescales between experimental and computational approaches that make correlated investigations arduous. Coarse-grained molecular dynamics simulations are used to investigate the dynamics of capsomeres of Hepatitis B virus in non-assembly and self-assembly conditions. Capsomeres are modeled as flexible structures rather than rigid bodies to accurately capture the elastic nature of the in vitro protein while retaining computational efficiency. The simulation results are correlated to data from charge detection mass spectrometry, which characterizes stable intermediate structures via the simultaneous detection of particle charge and mass-to-charge ratio. Solutions comprising of oligomers with 2-10 capsomeres observed in non-assembly conditions are computationally investigated. Under assembly conditions, the mechanism of formation of an intermediate structure that is 75% of the capsid mass is explored.