Global and Local Structural Changes of Protein Unfolding

Abstract

In the mean-field Ising model, the folding-unfolding behavior of a protein is regarded as an ensemble of units reduced from, presumably, peptide bonds or amino acid residues. Units of similar thermodynamic properties are further classified into groups that are related to, for instance, alpha-helices or beta-sheets. Units of the same group are assumed to unfold collectively, whereas those of different groups may undergo either sequential or coupled unfolding. The introduction of unfolding groups facilitates the description of non-collective local structural changes experimentally observed via a multi-group unfolding. We incorporate denaturants and temperature effects into the free energy expression of the protein upon dissolution in a specific environment at thermal equilibrium, and a model protein, cytochrome c, was examined. Results indicate that there are at least four unfolding groups induced unfolding of cytochrome c: two are related to the prosthetic heme group, whereas another two groups are a-helices and global nearly group, which largely account for global changes in protein morphology. The extracted thermodynamic parameters, on the basis of the Ising model, can closely predict unfolding behaviors of the proteins in compounded denaturing environments.