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

FEBS Lett. 2017 Oct;591(20):3265-3275. doi: 10.1002/1873-3468.12836. Epub 2017 Sep 21.


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.

Keywords: fast-folding peptides; molecular dynamics simulations; β-hairpin.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Kinetics
  • Models, Molecular
  • Molecular Dynamics Simulation*
  • NIMA-Interacting Peptidylprolyl Isomerase / chemistry*
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Domains
  • Protein Engineering*
  • Protein Folding*
  • Protein Unfolding
  • Quantum Theory
  • Spectrophotometry, Infrared
  • Thermodynamics


  • NIMA-Interacting Peptidylprolyl Isomerase
  • PIN1 protein, human