A Comparative Study of Protein Unfolding in Aqueous Urea and DMSO Solutions: Surface Polarity, Solvent Specificity and Sequence of Secondary Structure Melting

Elucidation of possible pathways between folded (native) and unfolded states of a protein is a challenging task, as the intermediates are often hard to detect. Here we alter the solvent environment in a controlled manner by choosing two different co-solvents of water, urea and dimethyl sulphoxide (DMSO), and study unfolding of four different proteins to understand the respective sequence of melting by computer simulation methods. We indeed find interesting differences in the sequence of melting of alpha-helices and beta-sheets in these two solvents. For example, at 8M urea solution, beta-sheet parts of a protein is found to unfold preferentially, followed by the unfolding of alpha helices. In contrast, 8M DMSO solution unfolds alpha helices first, followed by the separation of beta-sheets for majority of proteins. Sequence of unfolding events in four different /β proteins and also in chicken villin head piece (HP-36) both in urea and DMSO solution demonstrate that the unfolding pathways are determined jointly by relative exposure of polar and non-polar residues of a protein and the mode of molecular action of a solvent on that protein.