Denaturant <i>m</i> values and heat capacity changes: Relation to changes in accessible surface areas of protein unfolding

TLDR

Heat‑capacity changes in protein unfolding depend on accessible surface area, a relationship confirmed for the proteins studied. Denaturant m values, reflecting the free‑energy dependence on denaturant concentration, were compiled for many proteins. m values correlate strongly (R≈0.84–0.90) with solvent‑exposed surface area and also with heat‑capacity changes, indicating that exposed surface area is a key determinant for both parameters.

Abstract

Abstract Denaturant m values, the dependence of the free energy of unfolding on denaturant concentration, have been collected for a large set of proteins. The m value correlates very strongly with the amount of protein surface exposed to solvent upon unfolding, with linear correlation coefficients of R = 0.84 for urea and R = 0.87 for guanidine hydrochloride. These correlations improve to R = 0.90 when the effect of disulfide bonds on the accessible area of the unfolded protein is included. A similar dependence on accessible surface area has been found previously for the heat capacity change (ΔC p ), which is confirmed here for our set of proteins. Denaturant m values and heat capacity changes also correlate well with each other. For proteins that undergo a simple two‐state unfolding mechanism, the amount of surface exposed to solvent upon unfolding is a main structural determinant for both m values and Δ C p .