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

• Type of Material: Article
• Authors: Laura Zanetti-Polzi, Universita degli Studi dell'Aquila; Caitlin M. Davis, University of Illinois at Urbana-Champaign; Martin Gruebele, University of Illinois at Urbana-Champaign; Richard Dyer, Emory University; Andrea Amadei, Universita degli Studi di Roma Tor Vergata; Isabella Daidone, Universita degli Studi dell'Aquila
• Language: English
• Date: 2017-10-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Federation of European Biochemical Societies
• Final Published Version (URL): http://dx.doi.org/10.1002/1873-3468.12836
• Title of Journal or Parent Work: FEBS Letters
• ISSN: 0014-5793
• Volume: 591
• Issue: 20
• Start Page: 3265
• End Page: 3275
• Grant/Funding Information: CMD was supported by a postdoctoral fellowship provided by the Center for Physics in Living Cells, funded by NSF PHY 1430124.; LZP, ID and AA acknowledge the CINECA award IsC20 HHOP under the ISCRA initiative for the availability of high-performance computing resources and support.; This work was supported by the National Institutes of Health (NIH R01 GM093318 to MG and NIH R01 GM53640 to RBD).
• Keywords: fast-folding peptides; Spectrophotometry, Infrared; Protein Unfolding; Thermodynamics; Quantum Theory; Kinetics; Protein Conformation, beta-Strand; Protein Folding; β-hairpin; molecular dynamics simulations; Protein Domains; Models, Molecular; Protein Conformation, alpha-Helical; Protein Engineering; Molecular Dynamics Simulation; Amino Acid Motifs; NIMA-Interacting Peptidylprolyl Isomerase
• Research Categories: Biophysics, Medical; Chemistry, Biochemistry; Biology, Molecular

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.