Molecular Dynamics Characterization of the Free and Encapsidated RNA2 of CCMV with the oxRNA Model

Abstract

The cowpea chlorotic mottle virus (CCMV) has emerged as a model system to assess the balance between electrostatic and topological features of single‐stranded RNA viruses, specifically in the context of the viral self‐assembly. Yet, despite its biophysical significance, little structural data on the RNA content of the CCMV virion is available. Here, the conformational dynamics of the RNA2 fragment of CCMV was assessed via coarse‐grained molecular dynamics simulations, employing the oxRNA2 force field. The behavior of RNA2 was characterized both as a freely‐folding molecule and within a mean‐field depiction of the capsid. For the former, the role of the salt concentration, the temperature and of ad hoc constraints on the RNA termini was verified on the equilibrium properties of RNA2. For the latter, a multi‐scale approach was employed to derive a potential profile of the viral cavity from atomistic structures of the CCMV capsid in solution. The conformational ensembles of the encapsidated RNA2 were significantly altered with respect to the freely‐folding counterparts, as shown by the emergence of long‐range motifs and pseudoknots. Finally, the role of the N‐terminal tails of the CCMV subunits is highlighted as a critical feature in the construction of a proper electrostatic model of the CCMV capsid.