Jump to main content
Jump to site search


A quantitative connection of experimental and simulated folding landscapes by vibrational spectroscopy

Author affiliations

Abstract

For small molecule reaction kinetics, computed reaction coordinates often mimic experimentally measured observables quite accurately. Although nowadays simulated and measured biomolecule kinetics can be compared on the same time scale, a gap between computed and experimental observables remains. Here we directly compared temperature-jump experiments and molecular dynamics simulations of protein folding dynamics using the same observable: the time-dependent infrared spectrum. We first measured the stability and folding kinetics of the fastest-folding β-protein, the GTT35 WW domain, using its structurally specific infrared spectrum. The relaxation dynamics of the peptide backbone, β-sheets, turn, and random coil were measured independently by probing the amide I′ region at different frequencies. Next, the amide I′ spectra along folding/unfolding molecular dynamics trajectories were simulated by accurate mixed quantum/classical calculations. The simulated time dependence and spectral amplitudes at the exact experimental probe frequencies provided relaxation and folding rates in agreement with experimental observations. The calculations validated by experiment yield direct structural evidence for a rate-limiting reaction step where an intermediate state with either the first or second hairpin is formed. We show how folding switches from a more homogeneous (apparent two-state) process at high temperature to a more heterogeneous process at low temperature, where different parts of the WW domain fold at different rates.

Graphical abstract: A quantitative connection of experimental and simulated folding landscapes by vibrational spectroscopy

Back to tab navigation

Supplementary files

Publication details

The article was received on 24 Aug 2018, accepted on 02 Oct 2018 and first published on 03 Oct 2018


Article type: Edge Article
DOI: 10.1039/C8SC03786H
Citation: Chem. Sci., 2018, Advance Article
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    A quantitative connection of experimental and simulated folding landscapes by vibrational spectroscopy

    C. M. Davis, L. Zanetti-Polzi, M. Gruebele, A. Amadei, R. B. Dyer and I. Daidone, Chem. Sci., 2018, Advance Article , DOI: 10.1039/C8SC03786H

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements