IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0019791.html
   My bibliography  Save this article

Structural Heterogeneity and Quantitative FRET Efficiency Distributions of Polyprolines through a Hybrid Atomistic Simulation and Monte Carlo Approach

Author

Listed:
  • Martin Hoefling
  • Nicola Lima
  • Dominik Haenni
  • Claus A M Seidel
  • Benjamin Schuler
  • Helmut Grubmüller

Abstract

Förster Resonance Energy Transfer (FRET) experiments probe molecular distances via distance dependent energy transfer from an excited donor dye to an acceptor dye. Single molecule experiments not only probe average distances, but also distance distributions or even fluctuations, and thus provide a powerful tool to study biomolecular structure and dynamics. However, the measured energy transfer efficiency depends not only on the distance between the dyes, but also on their mutual orientation, which is typically inaccessible to experiments. Thus, assumptions on the orientation distributions and averages are usually made, limiting the accuracy of the distance distributions extracted from FRET experiments. Here, we demonstrate that by combining single molecule FRET experiments with the mutual dye orientation statistics obtained from Molecular Dynamics (MD) simulations, improved estimates of distances and distributions are obtained. From the simulated time-dependent mutual orientations, FRET efficiencies are calculated and the full statistics of individual photon absorption, energy transfer, and photon emission events is obtained from subsequent Monte Carlo (MC) simulations of the FRET kinetics. All recorded emission events are collected to bursts from which efficiency distributions are calculated in close resemblance to the actual FRET experiment, taking shot noise fully into account. Using polyproline chains with attached Alexa 488 and Alexa 594 dyes as a test system, we demonstrate the feasibility of this approach by direct comparison to experimental data. We identified cis-isomers and different static local environments as sources of the experimentally observed heterogeneity. Reconstructions of distance distributions from experimental data at different levels of theory demonstrate how the respective underlying assumptions and approximations affect the obtained accuracy. Our results show that dye fluctuations obtained from MD simulations, combined with MC single photon kinetics, provide a versatile tool to improve the accuracy of distance distributions that can be extracted from measured single molecule FRET efficiencies.

Suggested Citation

  • Martin Hoefling & Nicola Lima & Dominik Haenni & Claus A M Seidel & Benjamin Schuler & Helmut Grubmüller, 2011. "Structural Heterogeneity and Quantitative FRET Efficiency Distributions of Polyprolines through a Hybrid Atomistic Simulation and Monte Carlo Approach," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-19, May.
  • Handle: RePEc:plo:pone00:0019791
    DOI: 10.1371/journal.pone.0019791
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019791
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0019791&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0019791?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Benjamin Schuler & Everett A. Lipman & William A. Eaton, 2002. "Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy," Nature, Nature, vol. 419(6908), pages 743-747, October.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Wei Shi & Si Wei & Xin-xin Hu & Guan-jiu Hu & Cu-lan Chen & Xin-ru Wang & John P Giesy & Hong-xia Yu, 2013. "Identification of Thyroid Receptor Ant/Agonists in Water Sources Using Mass Balance Analysis and Monte Carlo Simulation," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-9, October.
    2. Manuel P Luitz & Anders Barth & Alvaro H Crevenna & Rainer Bomblies & Don C Lamb & Martin Zacharias, 2017. "Covalent dye attachment influences the dynamics and conformational properties of flexible peptides," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-18, May.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Mark F. Nüesch & Lisa Pietrek & Erik D. Holmstrom & Daniel Nettels & Valentin Roten & Rafael Kronenberg-Tenga & Ohad Medalia & Gerhard Hummer & Benjamin Schuler, 2024. "Nanosecond chain dynamics of single-stranded nucleic acids," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Ashish Joshi & Anuja Walimbe & Anamika Avni & Sandeep K. Rai & Lisha Arora & Snehasis Sarkar & Samrat Mukhopadhyay, 2023. "Single-molecule FRET unmasks structural subpopulations and crucial molecular events during FUS low-complexity domain phase separation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Zhaowei Liu & Haipei Liu & Andrés M. Vera & Byeongseon Yang & Philip Tinnefeld & Michael A. Nash, 2024. "Engineering an artificial catch bond using mechanical anisotropy," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Andreas Hartmann & Koushik Sreenivasa & Mathias Schenkel & Neharika Chamachi & Philipp Schake & Georg Krainer & Michael Schlierf, 2023. "An automated single-molecule FRET platform for high-content, multiwell plate screening of biomolecular conformations and dynamics," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Mingu Kang & Hyunwoo Kim & Elham Oleiki & Yeonjeong Koo & Hyeongwoo Lee & Huitae Joo & Jinseong Choi & Taeyong Eom & Geunsik Lee & Yung Doug Suh & Kyoung-Duck Park, 2022. "Conformational heterogeneity of molecules physisorbed on a gold surface at room temperature," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    6. Antonio B Oliveira Jr. & Francisco M Fatore & Fernando V Paulovich & Osvaldo N Oliveira Jr. & Vitor B P Leite, 2014. "Visualization of Protein Folding Funnels in Lattice Models," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-9, July.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0019791. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.