A Molecular View of the Dynamics of dsDNA Packing Inside Viral Capsids in the Presence of Ions.

Genome packing in viruses and prokaryotes relies on positively charged ions to reduce electrostatic repulsions, and induce attractions that can facilitate DNA condensation. Here we present molecular dynamics simulations spanning several microseconds of dsDNA packing inside nanometer-sized viral capsids. We use a detailed molecular model of DNA that accounts for molecular structure, basepairing, and explicit counterions. The size and shape of the capsids studied here are based on the 30-nanometer-diameter gene transfer agents of bacterium Rhodobacter capsulatus that transfer random 4.5-kbp (1.5 μm) DNA segments between bacterial cells. Multivalent cations such as spermidine and magnesium induce attraction between packaged DNA sites that can lead to DNA condensation. At high concentrations of spermidine, this condensation significantly increases the shear stresses on the packaged DNA while also reducing the pressure inside the capsid. These effects result in an increase in the packing velocity and the total amount of DNA that can be packaged inside the nanometer-sized capsids. In the simulation results presented here, high concentrations of spermidine did not produce the premature stalling observed in experiments. However, a small increase in the heterogeneity of packing velocities was observed in the systems with magnesium and spermidine ions compared to the system with only salt. The results presented here indicate that the effect of multivalent cations and of spermidine, in particular, on the dynamics of DNA packing, increases with decreasing packing velocities.