Parallel folding pathways of Fip35 WW domain explained by infrared spectra and their computer simulation

Laura Zanetti-Polzi, Caitlin M. Davis, Martin Gruebele, R. Brian Dyer, Andrea Amadei, Isabella Daidone

Research output: Contribution to journalLetter

Abstract

We present a calculation of the amide I′ infrared (IR) spectra of the folded, unfolded, and intermediate states of the WW domain Fip35, a model system for β-sheet folding. Using an all-atom molecular dynamics simulation in which multiple folding and unfolding events take place we identify six conformational states and then apply perturbed matrix method quantum-mechanical calculations to determine their amide I′ IR spectra. Our analysis focuses on two states previously identified as Fip35 folding intermediates and suggests that a three-stranded core similar to the folded state core is the main source of the spectroscopic differences between the two intermediates. In particular, we propose a hypothesis for why folding via one of these intermediates was not experimentally observed by IR T-jump.

Original languageEnglish (US)
Pages (from-to)3265-3275
Number of pages11
JournalFEBS Letters
Volume591
Issue number20
DOIs
StatePublished - Oct 2017

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Amides
Computer Simulation
Infrared radiation
Computer simulation
Molecular Dynamics Simulation
Molecular dynamics
Atoms

Keywords

  • fast-folding peptides
  • molecular dynamics simulations
  • β-hairpin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Parallel folding pathways of Fip35 WW domain explained by infrared spectra and their computer simulation. / Zanetti-Polzi, Laura; Davis, Caitlin M.; Gruebele, Martin; Dyer, R. Brian; Amadei, Andrea; Daidone, Isabella.

In: FEBS Letters, Vol. 591, No. 20, 10.2017, p. 3265-3275.

Research output: Contribution to journalLetter

Zanetti-Polzi, Laura ; Davis, Caitlin M. ; Gruebele, Martin ; Dyer, R. Brian ; Amadei, Andrea ; Daidone, Isabella. / Parallel folding pathways of Fip35 WW domain explained by infrared spectra and their computer simulation. In: FEBS Letters. 2017 ; Vol. 591, No. 20. pp. 3265-3275.
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AU - Daidone, Isabella

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