Stabilization of proteins in confined spaces

We present theory showing that confining a protein to a small inert space ( a "cage") should stabilize the protein against reversible unfolding. Exampl es of such spaces might include the pores within chromatography columns, th e Anfinsen cage in chaperonins, the interiors of ribosomes, or regions of s teric occlusion inside cells. Confinement eliminates some expanded configur ations of the unfolded chain, shifting the equilibrium from the unfolded st ate toward the native state. The partition coefficient for a protein in a c onfined space is predicted to decrease significantly when the solvent is ch anged from native to denaturing conditions. Small cages are predicted to in crease the stability of the native state by as much as 15 kcal/mol. Confine ment may also increase the rates of protein or RNA folding.