Complete Virion Simulated: All-Atom Model of an MS2 Bacteriophage with Native Genome

Abstract

For the first time, a complete all-atom molecular dynamics (MD) model of a virus, bacteriophage MS2, in its entirety, including a protein outer shell, native genomic RNA with necessary divalent ions, and surrounding explicit aqueous solution with ions at physiological concentration, was built. The model is based on an experimentally measured cryo-EM structure, which was substantially augmented by reconstructing missing or low-resolution parts of the measured density (where the atomistic structure cannot be fit unambiguously). The model was tested by a quarter of a microsecond MD run, and various biophysical characteristics are obtained and analyzed. The developed methodology of building the model can be used for reconstructing other large biomolecular structures when experimental data are fragmented and/or of varying resolution, while the model itself can be used for studying the biology of MS2, including the dynamics of its interaction with the host bacteria.

Exploring the Effects of Intersubunit Interface Mutations on Virus-Like Particle Structure and Stability

“…The full capsid and complete virion of MS2 with its native genome have been studied using all-atom molecular dynamics, revealing useful information about RNA-capsid interactions. − However, full capsid all-atom simulations are computationally intensive, and corresponding coarse-grained simulations may not allow the study of interactions between specific residues or atoms. Given the biological relevance and smaller sizes of the 6CP2 and 10CP2 assembly intermediates, we decided to use these input structures for molecular dynamics simulations.…”

Context-dependent structure formation of hairpin motifs in bacteriophage MS2 genomic RNA

“…Many simple +ssRNA viruses consisting solely of a proteinaceous capsid and viral gRNA have been shown to utilize one or more PS motifs to selectively package their genomes [22][23][24][25][26][27][28], even though the presence and functionality of these motifs are often difficult to establish [20]. One of the most well-studied viral systems in this respect is bacteriophage MS2, a small +ssRNA virus that infects bacteria [26,27,[29][30][31][32][33][34][35]. Based on theoretical analyses, its self-assembly has been proposed to follow a Hamiltonian path [28,36] which hinges on the presence of numerous PS motifs along its genome [37,38].…”