The structure and dynamics of a fully packaged RNA virus.

Abstract

The vast majority of known viruses that infect humans have their genetic program written in molecules of RNA. Such RNA viruses are thought to attain their final, mature form via self-assembly of individual capsid proteins directed by specific interactions with the RNA genome. Despite tremendous amount of experimental information about the average structure of the protein capsids, much less is known about the structure and dynamics of the RNA genomes. Here, we characterized the structure, dynamics and ion atmosphere in a bacteriophage MS2 virus using all-atom molecular dynamics simulations. Starting from available experimental information, we built a computational model of a mature MS2 virion containing a 3569 nucleotide RNA genome enclosed inside a mature protein capsid that in turn consists of a single maturation protein embedded within an icosahedral lattice of the protein capsid. Our two 2.5-microsecond replica simulations of the complete virion differing by the initial configurations of the RNA genome revealed the stabilizing effect of the RNA—protein interactions on the structure of the mature capsid and on the conformation of the RNA genome. The virus particle as a whole was observed to undergo a breathing-like motion, whereas parts of the RNA genome not bound specifically to the protein capsid explored a range of structural transformations while retaining their secondary structure. A set of simulations performed upon removal of the RNA genome characterized the effect of the RNA on the internal pressure in the virus and on its ion atmosphere. Taken together, our work introduces a mature viral particle as a system of high dynamic complexity where repulsive RNA-RNA interactions compete with specific RNA-protein binding, with the ion atmosphere serving as intermolecular glue holding the assembly together.