  Most proteins must remain soluble in the cytosol in order to perform their
biological functions. To protect against undesired protein aggregation, living
cells maintain a population of molecular chaperones that ensure the solubility
of the proteome. Here we report simulations of a lattice model of interacting
proteins to understand how low concentrations of passive molecular chaperones,
such as small heat-shock proteins, suppress thermodynamic instabilities in
protein solutions. Given fixed concentrations of chaperones and client
proteins, the solubility of the proteome can be increased by tuning the
chaperone--client binding strength. Surprisingly, we find that the binding
strength that optimizes solubility while preventing irreversible chaperone
binding also promotes the formation of weakly bound chaperone oligomers,
although the presence of these oligomers does not significantly affect the
thermodynamic stability of the solution. Such oligomers are commonly observed
in experiments on small heat-shock proteins, but their connection to the
biological function of these chaperones has remained unclear. Our simulations
suggest that this clustering may not have any essential biological function,
but rather emerges as a natural side-effect of optimizing the thermodynamic
stability of the proteome.
