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Parallel folding pathways of Fip35 WW domain explained by infrared spectra and their computer simulation
Author(s) -
ZanettiPolzi Laura,
Davis Caitlin M.,
Gruebele Martin,
Dyer R. Brian,
Amadei Andrea,
Daidone Isabella
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12836
Subject(s) - folding (dsp implementation) , ww domain , infrared , protein folding , spectral line , chemistry , domain (mathematical analysis) , chemical physics , biophysics , crystallography , physics , biology , biochemistry , engineering , optics , mathematics , mathematical analysis , astronomy , electrical engineering , gene
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.