On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.

FSD-1, a designed small ultrafast folder with a ββα fold, has been actively studied in the last few years as a model system for studying protein folding mechanisms and for testing of the accuracy of computational models. The suitability of this protein to describe the folding of naturally occurring...

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Autores principales:	Chun Wu, Joan-Emma Shea
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0daefdc7d4c541daa1e6c5123e5ba43c
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spelling	oai:doaj.org-article:0daefdc7d4c541daa1e6c5123e5ba43c2021-11-18T05:51:54ZOn the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.1553-734X1553-735810.1371/journal.pcbi.1000998https://doaj.org/article/0daefdc7d4c541daa1e6c5123e5ba43c2010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21124953/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358FSD-1, a designed small ultrafast folder with a ββα fold, has been actively studied in the last few years as a model system for studying protein folding mechanisms and for testing of the accuracy of computational models. The suitability of this protein to describe the folding of naturally occurring α/β proteins has recently been challenged based on the observation that the melting transition is very broad, with ill-resolved baselines. Using molecular dynamics simulations with the AMBER protein force field (ff96) coupled with the implicit solvent model (IGB = 5), we shed new light into the nature of this transition and resolve the experimental controversies. We show that the melting transition corresponds to the melting of the protein as a whole, and not solely to the helix-coil transition. The breadth of the folding transition arises from the spread in the melting temperatures (from ∼325 K to ∼302 K) of the individual transitions: formation of the hydrophobic core, β-hairpin and tertiary fold, with the helix formed earlier. Our simulations initiated from an extended chain accurately predict the native structure, provide a reasonable estimate of the transition barrier height, and explicitly demonstrate the existence of multiple pathways and multiple transition states for folding. Our exhaustive sampling enables us to assess the quality of the Amber ff96/igb5 combination and reveals that while this force field can predict the correct native fold, it nonetheless overstabilizes the α-helix portion of the protein (Tm = ∼387K) as well as the denatured structures.Chun WuJoan-Emma SheaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 6, Iss 11, p e1000998 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Chun Wu Joan-Emma Shea On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.
description	FSD-1, a designed small ultrafast folder with a ββα fold, has been actively studied in the last few years as a model system for studying protein folding mechanisms and for testing of the accuracy of computational models. The suitability of this protein to describe the folding of naturally occurring α/β proteins has recently been challenged based on the observation that the melting transition is very broad, with ill-resolved baselines. Using molecular dynamics simulations with the AMBER protein force field (ff96) coupled with the implicit solvent model (IGB = 5), we shed new light into the nature of this transition and resolve the experimental controversies. We show that the melting transition corresponds to the melting of the protein as a whole, and not solely to the helix-coil transition. The breadth of the folding transition arises from the spread in the melting temperatures (from ∼325 K to ∼302 K) of the individual transitions: formation of the hydrophobic core, β-hairpin and tertiary fold, with the helix formed earlier. Our simulations initiated from an extended chain accurately predict the native structure, provide a reasonable estimate of the transition barrier height, and explicitly demonstrate the existence of multiple pathways and multiple transition states for folding. Our exhaustive sampling enables us to assess the quality of the Amber ff96/igb5 combination and reveals that while this force field can predict the correct native fold, it nonetheless overstabilizes the α-helix portion of the protein (Tm = ∼387K) as well as the denatured structures.
format	article
author	Chun Wu Joan-Emma Shea
author_facet	Chun Wu Joan-Emma Shea
author_sort	Chun Wu
title	On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.
title_short	On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.
title_full	On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.
title_fullStr	On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.
title_full_unstemmed	On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.
title_sort	on the origins of the weak folding cooperativity of a designed ββα ultrafast protein fsd-1.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/0daefdc7d4c541daa1e6c5123e5ba43c
work_keys_str_mv	AT chunwu ontheoriginsoftheweakfoldingcooperativityofadesignedbbaultrafastproteinfsd1 AT joanemmashea ontheoriginsoftheweakfoldingcooperativityofadesignedbbaultrafastproteinfsd1
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On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.

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