title: Radical Formation Initiates Solvent-Dependent Unfolding and β-sheet Formation in a Model Helical Peptide.
abstract: We examined the effects of Cα-centered radical formation on the stability of a model helical peptide, N-Ac-KK(AL)10KK-NH2. Three, 100 ns molecular dynamics simulations using the OPLS-AA force field were carried out on each α-helical peptide in six distinct binary TIP4P water/2,2,2-trifluoroethanol (TFE) mixtures. The α-helicity was at a maximum in 20% TFE, which was inversely proportional to the number of H-bonds between water molecules and the peptide backbone. The radial distribution of TFE around the peptide backbone was highest in 20% TFE, which enhanced helix stability. The Cα-centered radical initiated the formation of a turn within 5 ns, which was a smaller kink at high TFE concentrations, and a loop at lower TFE concentrations. The highest helicity of the peptide radical was measured in 100% TFE. The formation of hydrogen bonds between the peptide backbone and water destabilized the helix, whereas the clustering of TFE molecules around the radical center stabilized the helix. Following radical termination, the once helical structure converted to a β-sheet rich state in 100% water only, and this transition did not occur in the nonradical control peptide. This study gives evidence on how the formation of peptide radicals can initiate α-helical to β-sheet transitions under oxidative stress conditions.
authors.affiliation: Institute of Complex Systems: Structural Biochemistry (ICS-6), Forschungszentrum Jülich , 52425 Jülich, Germany.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Owen
authors.affiliation: Institute of Complex Systems: Structural Biochemistry (ICS-6), Forschungszentrum Jülich , 52425 Jülich, Germany.|Institute of Theoretical and Computational Chemistry, Heinrich Heine University Düsseldorf , Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Strodel
authors.affiliation: Department of Chemistry, University of Toronto , Toronto, ON Canada M5S 3H6.|Institute of Chemistry, Faculty of Material Science, University of Miskolc , Egyetemváros 1, H-3529 Miskolc, Hungary.|Drug Discovery Research Center , 6720 Szeged, Hungary.
authors.forename: Imre G
authors.initials: IG
authors.lastname: Csizmadia
authors.affiliation: Institute of Chemistry, Faculty of Material Science, University of Miskolc , Egyetemváros 1, H-3529 Miskolc, Hungary.|Drug Discovery Research Center , 6720 Szeged, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Viskolcz
mesh_terms: D000595:Amino Acid Sequence; D016000:Cluster Analysis; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D012997:Solvents / Q000737:chemistry*; D014270:Trifluoroethanol / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; D012997:Solvents; D014867:Water; D014270:Trifluoroethanol