in silico Binding Free Energy Characterization of Cowpea Chlorotic Mottle Virus Coat Protein Homodimer Variants

The viral capsid’s main function is to transport and protect its nucleic acid. It is formed by the self-assembly of multiple copies of one, or a few, coat proteins (CP). The molecular mechanisms of how the spontaneous self-assembly process takes place still remains obscure. Cowpea Chlorotic Mottle Virus (CCMV), an icosahedral plant pathogen, was used as model for understanding the assembly of symmetrical aggregates of biomolecules. Six potential key residues in the capsid interfaces of CCMV were identfied. in silico free energy of binding was estimated for two functional CP dimers; WT and the sextuple mutant. Our results show that perturbation of these specific residues will likely destabilize the capsid structure as a whole. This provides insights into how viral coat proteins recognize each other inside the cell, and suggest ways to develop mechanisms to prevent their assembly, thereby blocking the infection.