title: Smoothing of the GB1 hairpin folding landscape by interfacial confinement.
abstract: We study the effects of confinement between planar walls on the folding thermodynamics of a β-hairpin, using large-scale replica-exchange molecular-dynamics simulations with an all-atom model and explicit solvent. We find that the folding free-energy landscape of this peptide observed in bulk is significantly modified when the peptide is confined between the walls. Most notably, the propensity of the peptide to form a misfolded state observed in the bulk solution becomes negligible under confinement. The absence of the misfolded state under confinement can be explained by an increased tendency of hydrophobic aromatic side chains to stay near the walls, because the misfolded state is characterized by a nonnative arrangement of aromatic side chains. These results from a simple confinement model may provide clues about the role of chaperonin confinement in smoothing folding landscapes by avoiding trapped intermediates.
authors.affiliation: Department of Chemical Engineering, Lehigh University, Bethlehem, Pennsylvania.
authors.forename: Apratim
authors.initials: A
authors.lastname: Bhattacharya
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Best
authors.affiliation: Department of Chemical Engineering, Lehigh University, Bethlehem, Pennsylvania. Electronic address: jeetain@lehigh.edu.
authors.forename: Jeetain
authors.initials: J
authors.lastname: Mittal
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D012997:Solvents