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 an exemplary model system to assess the balance between electrostatic and topological features of ssRNA viruses, specifically in the context of the viral self-assembly process. Yet, in spite of its biophysical significance, little structural data of the RNA content of the CCMV virion is currently available. Here, the conformational dynamics of the RNA2 fragment of CCMV was assessed via coarse-grained molecular dynamics simulations, employing the oxRNA2 model. The behavior of RNA2 has been characterized both as a freely-folding molecule and within a mean-field depiction of a CCMV-like capsid. For the latter, a multi-scale approach was employed, to derive a radial 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 in the former case. Finally, the role of the N-terminal tails of the CCMV subunits (and ionic shells thereof) is highlighted as a critical feature in the construction of a proper electrostatic model of the CCMV capsid.