title: Comparative study of protein unfolding in aqueous urea and dimethyl sulfoxide solutions: surface polarity, solvent specificity, and sequence of secondary structure melting.
abstract: 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 cosolvents of water, urea, and dimethyl sulfoxide (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 α helices and β sheets in these two solvents. For example, in 8 M urea solution, β-sheet parts of a protein are found to unfold preferentially, followed by the unfolding of α helices. In contrast, 8 M DMSO solution unfolds α helices first, followed by the separation of β sheets for the majority of proteins. Sequence of unfolding events in four different α/β proteins and also in chicken villin head piece (HP-36) both in urea and DMSO solutions demonstrate that the unfolding pathways are determined jointly by relative exposure of polar and nonpolar residues of a protein and the mode of molecular action of a solvent on that protein.
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Susmita
authors.initials: S
authors.lastname: Roy
authors.forename: Biman
authors.initials: B
authors.lastname: Bagchi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D002645:Chickens; D003198:Computer Simulation; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D001467:Hordeum / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D016900:Neurofilament Proteins / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry*; D025801:Ubiquitin / Q000737:chemistry; D014508:Urea / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D010455:Peptides; D010940:Plant Proteins; D011506:Proteins; D025801:Ubiquitin; C093336:chymotrypsin inhibitor 2; C115223:villin headpiece subdomain peptide; D014508:Urea; D004121:Dimethyl Sulfoxide