title: Protein folding under confinement: a role for solvent.
abstract: Although most experimental and theoretical studies of protein folding involve proteins in vitro, the effects of spatial confinement may complicate protein folding in vivo. In this study, we examine the folding dynamics of villin (a small fast folding protein) with explicit solvent confined to an inert nanopore. We have calculated the probability of folding before unfolding (P(fold)) under various confinement regimes. Using P(fold) correlation techniques, we observed two competing effects. Confining protein alone promotes folding by destabilizing the unfolded state. In contrast, confining both protein and solvent gives rise to a solvent-mediated effect that destabilizes the native state. When both protein and solvent are confined we see unfolding to a compact unfolded state different from the unfolded state seen in bulk. Thus, we demonstrate that the confinement of solvent has a significant impact on protein kinetics and thermodynamics. We conclude with a discussion of the implications of these results for folding in confined environments such as the chaperonin cavity in vivo.
authors.affiliation: Biophysics Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Del
authors.initials: D
authors.lastname: Lucent
authors.forename: V
authors.initials: V
authors.lastname: Vishal
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012997:Solvents / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D008840:Microfilament Proteins; D012997:Solvents; C026615:villin; D010649:Phenylalanine