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Issue 14, 2017
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Dimerization and conformation-related free energy landscapes of dye-tagged amyloid-β12–28 linked to FRET experiments

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Abstract

We have investigated the free energy landscape of Aβ-peptide dimer models in connection to gas-phase FRET experiments. We use a FRET-related distance coordinate and one conformation-related coordinate per monomer for accelerated structural exploration with well-tempered metadynamics in solvent and in vacuo. The free energy profiles indicate that FRET under equilibrium conditions should be significantly affected by the de-solvation upon the transfer of ions to the gas-phase. In contrast, a change in the protonation state is found to be less impacting once de-solvated. Comparing F19P and WT alloforms, for which we measure different FRET efficiencies in the gas-phase, we predict only the relevant structural differences in the solution populations, not under gas-phase equilibrium conditions. This finding supports the hypothesis that the gas-phase action-FRET measurement after ESI operates under non-equilibrium conditions, with a memory of the solution conditions – even for the dimer of this relatively short peptide. The structural differences in solution are rationalized in terms of conformational propensities around residue 19, which show a transition to a poly-proline type of pattern upon mutation to F19P – a difference that gets lost in the gas-phase.

Graphical abstract: Dimerization and conformation-related free energy landscapes of dye-tagged amyloid-β12–28 linked to FRET experiments

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Publication details

The article was received on 27 Jan 2017, accepted on 13 Mar 2017 and first published on 13 Mar 2017


Article type: Paper
DOI: 10.1039/C7CP00611J
Citation: Phys. Chem. Chem. Phys., 2017,19, 9470-9477
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    Dimerization and conformation-related free energy landscapes of dye-tagged amyloid-β12–28 linked to FRET experiments

    A. Kulesza, S. Daly and P. Dugourd, Phys. Chem. Chem. Phys., 2017, 19, 9470
    DOI: 10.1039/C7CP00611J

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