Small icosahedral viruses have a compact capsid that apparently lacks holes through which solvents can be exchanged with the external milieu. However, due to the steric hindrance of amino acids, upon folding, capsid proteins form narrow cavities in which water and ions can be trapped. These occluded solvent molecules can form lines of water, called water wires, representing an arrangement with special features for proton conduction. In this chapter, we review the physico-chemical principles that permit proton conduction through protein cavities. We also describe how a combination of these elements found in an insect viral capsid can allow the virus to sense alkaline environments. Through this analysis, we stress the need to combine experimental and theoretical techniques when modeling complex biological systems.
Keywords: Grotthuss; Proton diode; Triatoma virus; Water wire; pH sensing.