title: Role of solvation effects in protein denaturation: from thermodynamics to single molecules and back.
abstract: Protein stability often is studied in vitro through the use of urea and guanidinium chloride, chemical cosolvents that disrupt protein native structure. Much controversy still surrounds the underlying mechanism by which these molecules denature proteins. Here we review current thinking on various aspects of chemical denaturation. We begin by discussing classic models of protein folding and how the effects of denaturants may fit into this picture through their modulation of the collapse, or coil-globule transition, which typically precedes folding. Subsequently, we examine recent molecular dynamics simulations that have shed new light on the possible microscopic origins of the solvation effects brought on by denaturants. It seems likely that both denaturants operate by facilitating solvation of hydrophobic regions of proteins. Finally, we present recent single-molecule fluorescence studies of denatured proteins, the analysis of which corroborates the role of denaturants in shifting the equilibrium of the coil-globule transition.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: England
authors.forename: Gilad
authors.initials: G
authors.lastname: Haran
mesh_terms: D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D019791:Guanidine / Q000737:chemistry* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation / Q000187:drug effects; D011489:Protein Denaturation / Q000187:drug effects*; D017510:Protein Folding / Q000187:drug effects*; D017433:Protein Structure, Secondary / Q000187:drug effects; D011506:Proteins / Q000737:chemistry; D012997:Solvents / Q000737:chemistry* / Q000494:pharmacology; D013816:Thermodynamics; D014508:Urea / Q000737:chemistry / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D011506:Proteins; D012997:Solvents; D014867:Water; D014508:Urea; D019791:Guanidine