Molecular Dynamics Simulations of Elastic Capsomeres Self Assembling into a Virus Capsid*

Viruses are an important class of soft biological materials that are capable of self-assembling into capsids that are often icosahedral-shaped. However, this self-assembly process is not completely understood in part due to the arduousness and simulation cost of correlated investigations between experiments and rigid-body models of constituent capsomere subunits. Experimentally-informed, hybrid OpenMP/MPI parallelized molecular dynamics simulations of a coarse-grained model composed of elastic capsomeres are used to investigate the assembly pathway of heterogeneous icosahedral viruses, focusing on Hepatitis B virus (HBV) as a first application. Simulation results are correlated to data from charge detection mass spectrometry. Based on the time-dependent mass spectrums and steady-state phase diagrams associated with the self-assembly of HBV at 5-100 micromolar protein and 100-500 millimolar salt concentrations, we propose that the formation of both 90- and 120-capsomere (T3, T4) structures in HBV can be attributed to relatively low bending modulus of HBV capsomeres (10-15 kB T). Further, HBV self-assembly exhibits hierarchical features for small (<120 capsomere) icosahedral structures.