ARTICLE: Computer viruses of the biological kind

Modelling the self-assembly of virus capsids

• Viruses self-assemble protective protein coats that are important for their survival and proliferation: we use computer simulation to explore how this self-assembly takes place in the noisy environment of the cell, learning both about central viral processes and more general self-assembly principles

Virus capsids are protein coats that surround and protect the genetic information of a virus. Viruses have a range of different structures: many common ones are icosahedral, with structures like those of (UK) footballs, or the Eden Project. In this paper in Journal of Physics: Condensed Matter here (and on the cover! and free here), we use physics and computer simulation to investigate how virus capsids form in unfortunate host cells. 

The capsids we consider self-assemble -- that is, they form from interacting subunits with no external guidance. These subunits are made of proteins, parts of which chemically stick to each other. The shape of these subunits, and the geometry of the sticky patches, is vital in determining the final capsid structure.

We used a model for capsid assembly that had been explored previously in an "energy landscape" picture -- considering a huge range of possible arrangements of subunits, and identifying which structures were the most energetically favourable. Ideally, a perfect capsid -- with the subunits arranged in an icosahedron -- should be at the bottom of an energetic "valley" -- all other arrangements should naturally "fall" towards that structure. If the landscape is too flat, the subunits may never fall far enough into the valley to form the icosahedron; if it's too rugged, they may fall into another hole (corresponding to a malformed capsid structure) and get stuck. A related important factor is temperature: if the temperature is too high, proteins will whizz around and never manage to stick; if too low, they may stick and "freeze" in the wrong arrangements.

A snapshot of a simulation where viruses are assembling from proteins (red and green) in the presence of cellular crowding agents (yellow). Some have formed completely; other proteins have not yet met partners with which to bond.

Using computer simulations, we explored how model protein shape, density, and temperature affected capsids' ability to assemble correctly. We demonstrated the "sweet spots" for proteins of different shapes (too cold/sticky gives malformed structures, too hot/unsticky cannot form bonds). We showed that the presence of other stuff in the cell (cells are very crowded) interferes with assembly in idealised circumstances, but can enhance assembly by forcing proteins closer together when protein density is low (there's a video of self-assembly simulations here). We saw that viruses can assemble through rather complex dynamics, involving folding and reorganisation of half-formed structures. As well as complementing the "energy landscape" picture of self-assembly, these insights may help us design ways of interfering with capsid assembly and thus making things harder for viruses. Iain