Hamiltonian path analysis of viral genomes

Cryo-electron microscopy (EM) is undergoing a revolution, enabling the study of viral pathogens in unprecedented detail. The asymmetric EM reconstruction of bacteriophage MS2 at medium resolution (8.7 Å) by Koning et al.1, and the subsequent reconstruction at even higher resolution (3.6 Å) by Dai et al.2 revealed the structures of both the protein shell and the asym- metric genomic RNA and the unique maturation protein (A). It is the start of a wave of such structural data for viruses, and calls for the development of new analytical tools to describe the results. One approach is Hamiltonian path analysis (HPA) that we introduced to describe repeated, sequence-specific contacts between the MS2 genome and its protein shell3. Here, we describe how HPA is consistent with the new structures and, in turn, how it extends our understanding beyond the structural data alone.