title: The structure of chromophore-grafted amyloid-β(12-28) dimers in the gas-phase: FRET-experiment guided modelling.
abstract: We present theoretical modelling, ion mobility spectrometry and action-FRET experiments for chromophore-grafted amyloid-β(12-28) dimers. A first-principles global minimum search based on replica-exchange molecular dynamics (REMD) leads to a compact structure with strong interstrand interactions. We use REMD with a distance restraint that implements an adaptive effective bias upon average FRET-efficiencies and thus guides the sampling by the action-FRET measurement. This procedure leads to a pair of weakly interacting peptides. Ion-mobility confirms that the weakly interacting structure and not the global minimum with strongly interacting peptides is populated in the experiment. The presence of a high energy barrier between the two structural families, as evidenced from the MD data, suggests that a kinetically trapped structure is observed in the experiment.
authors.affiliation: Université de Lyon, F-69622 Lyon, France. philippe.dugourd@univ-lyon1.fr and Institut Lumière Matière, UMR5306, CNRS, Université Lyon 1, 69622 Villeurbanne, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kulesza
authors.affiliation: Université de Lyon, F-69622 Lyon, France. philippe.dugourd@univ-lyon1.fr and Institut Lumière Matière, UMR5306, CNRS, Université Lyon 1, 69622 Villeurbanne, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Daly
authors.affiliation: Université de Lyon, F-69622 Lyon, France. philippe.dugourd@univ-lyon1.fr and Institut Lumière Matière, UMR5306, CNRS, Université Lyon 1, 69622 Villeurbanne, France.
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Choi
authors.affiliation: Université de Lyon, F-69622 Lyon, France. philippe.dugourd@univ-lyon1.fr and Institut Lumière Matière, UMR5306, CNRS, Université Lyon 1, 69622 Villeurbanne, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Simon
authors.affiliation: Université de Lyon, F-69622 Lyon, France. philippe.dugourd@univ-lyon1.fr and Institut des Sciences Analytiques, UMR5280, CNRS, Université Lyon 1, 69100 Villeurbanne, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Chirot
authors.affiliation: Université de Lyon, F-69622 Lyon, France. philippe.dugourd@univ-lyon1.fr and Institut Lumière Matière, UMR5306, CNRS, Université Lyon 1, 69622 Villeurbanne, France.
authors.forename: Luke
authors.initials: L
authors.lastname: MacAleese
authors.affiliation: Université de Lyon, F-69622 Lyon, France. philippe.dugourd@univ-lyon1.fr and Institut Lumière Matière, UMR5306, CNRS, Université Lyon 1, 69622 Villeurbanne, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Antoine
authors.affiliation: Université de Lyon, F-69622 Lyon, France. philippe.dugourd@univ-lyon1.fr and Institut Lumière Matière, UMR5306, CNRS, Université Lyon 1, 69622 Villeurbanne, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dugourd
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C092395:amyloid beta-protein (12-28)