title: Structural exploration and Förster theory modeling for the interpretation of gas-phase FRET measurements: Chromophore-grafted amyloid-β peptides.
abstract: The distance-dependence of excitation energy transfer, e.g., being described by Förster theory (Förster resonance energy transfer (FRET)), allows the use of optical techniques for the direct observation of structural properties. Recently, this technique has been successfully applied in the gas phase. The detailed interpretation of the experimental FRET results, however, relies on the comparison with structural modeling. We therefore present a complete first-principles modeling approach that explores the gas-phase structure of chromophore-grafted peptides and achieves accurate predictions of FRET efficiencies. We apply the approach to amyloid-β 12-28 fragments, known to be involved in amyloid plaque formation connected to Alzheimer's disease. We sample structures of the peptides that are grafted with 5-carboxyrhodamine 575 (Rh575) and QSY-7 chromophores by means of replica-exchange molecular dynamics simulations upon an Amber-type forcefield parametrization as a function of the charge state. The generated ensembles provide chromophore-distance and -orientation distributions which are used with the spectral parameters of the Rh575/QSY-7 chromophores to model FRET-efficiencies for the systems. The theoretical values agree with the experimental average "action"-FRET efficiencies and motivate to use the herein reported parametrization, sampling, and FRET-modeling technique in future studies on the structural properties and aggregation-behavior of related systems.
authors.affiliation: Institut Lumière Matière, UMR5306 Université Claude Bernard Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kulesza
authors.affiliation: Institut Lumière Matière, UMR5306 Université Claude Bernard Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Daly
authors.affiliation: Institut Lumière Matière, UMR5306 Université Claude Bernard Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: Luke
authors.initials: L
authors.lastname: MacAleese
authors.affiliation: Institut Lumière Matière, UMR5306 Université Claude Bernard Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Antoine
authors.affiliation: Institut Lumière Matière, UMR5306 Université Claude Bernard Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dugourd
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D005740:Gases / Q000737:chemistry*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D005740:Gases; D010446:Peptide Fragments; D012235:Rhodamines; C092395:amyloid beta-protein (12-28)