Biophysical Journal 90 5

Cover picture: Population distribution for two proteins, a fragment of Protein A (top) and the SH3 domain of the SRC protein kinase (bottom), in bulk (left) and in confined (right) environments, as obtained by the density-of-states Monte Carlo simulations. The x axes represent radii of gyration (Rg) and the y axes depict fraction of native structure (Q) present in protein conformations. Confining a protein inside a spherical cavity reduces the entropy of the unfolded state resulting in the stabilization of the native state. The extent of this entropic stabilization is dependent not only on the protein size and degree of confinement but also on the specific topology of the protein. The broader landscape for SH3 in comparison to Protein A in the bulk implies that SH3 unfolded states have a larger size (Rg) and hence can be stabilized to a greater extent by confinement. See the article by Rathore et al. on page 1767.