Remarkably, perhaps 30% of expressed proteins are predicted to be unfolded. It is clear that a significant fraction of these are truly "intrinsically" unfolded but are simply unstable suggesting that they have evolved to take advantage of the stabilization provided excluded volume effects due to the tight packing of macromolecules in the cellular millieu. Obviously this makes it difficult to study the structural properties of these proteins in vitro, particularly in the NMR tube. Using the defined internal volume of the reverse micelle, we have developed this as a means to impart additional stability to an otherwise only marginally stable protein. The internal volume of a reverse micelle can be largely controlled by the amount of water that is provided. The nice thing about this approach is that in principle the native folded state is not only the best packed but also, through the thermodynamic hypothesis, the most stable.
Thus a properly sized reverse micelle will leave the free energy and structure of the native state alone but will destabilize the more extensive partially unfolded states causing the population to shift towards the desired folded native state. We have demonstrated this idea with a purposefully destabilized three helix bundle where the internal core is left unperturbed (i.e. can fold) but the helical propensity is decreased by surface mutations. Decreasing the water content ("loading") and corresponding decreasing the internal volume available to the protein causes it to fold (below figure).
See Peterson et al. (2004) JACS for more detail.