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

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 ?-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.

SUBMITTER: Zanetti-Polzi L

PROVIDER: S-EPMC5658256 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Zanetti-Polzi Laura L Davis Caitlin M CM Gruebele Martin M Dyer R Brian RB Amadei Andrea A Daidone Isabella I

FEBS letters 20170921 20

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 ...[more]

PMID: 28881468

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