A computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.

<h4>Background</h4>Amyloid fibril formation is the hallmark of many human diseases, including Alzheimer's disease, type II diabetes and amyloidosis. Amyloid fibrils deposit in the extracellular space and generally co-localize with the glycosaminoglycans (GAGs) of the basement membra...

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Autores principales:	Elodie Monsellier, Matteo Ramazzotti, Niccolò Taddei, Fabrizio Chiti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3bb64fc85d6b4834a1577cb347d59b35
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spelling	oai:doaj.org-article:3bb64fc85d6b4834a1577cb347d59b352021-12-02T20:20:26ZA computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.1932-620310.1371/journal.pone.0011363https://doaj.org/article/3bb64fc85d6b4834a1577cb347d59b352010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20613870/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Amyloid fibril formation is the hallmark of many human diseases, including Alzheimer's disease, type II diabetes and amyloidosis. Amyloid fibrils deposit in the extracellular space and generally co-localize with the glycosaminoglycans (GAGs) of the basement membrane. GAGs have been shown to accelerate the formation of amyloid fibrils in vitro for a number of protein systems. The high number of data accumulated so far has created the grounds for the construction of a database on the effects of a number of GAGs on different proteins.<h4>Methodology/principal findings</h4>In this study, we have constructed such a database and have used a computational approach that uses a combination of single parameter and multivariate analyses to identify the main chemical factors that determine the GAG-induced acceleration of amyloid formation. We show that the GAG accelerating effect is mainly governed by three parameters that account for three-fourths of the observed experimental variability: the GAG sulfation state, the solute molarity, and the ratio of protein and GAG molar concentrations. We then combined these three parameters into a single equation that predicts, with reasonable accuracy, the acceleration provided by a given GAG in a given condition.<h4>Conclusions/significance</h4>In addition to shedding light on the chemical determinants of the protein:GAG interaction and to providing a novel mathematical predictive tool, our findings highlight the possibility that GAGs may not have such an accelerating effect on protein aggregation under the conditions existing in the basement membrane, given the values of salt molarity and protein:GAG molar ratio existing under such conditions.Elodie MonsellierMatteo RamazzottiNiccolò TaddeiFabrizio ChitiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 6, p e11363 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elodie Monsellier Matteo Ramazzotti Niccolò Taddei Fabrizio Chiti A computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.
description	<h4>Background</h4>Amyloid fibril formation is the hallmark of many human diseases, including Alzheimer's disease, type II diabetes and amyloidosis. Amyloid fibrils deposit in the extracellular space and generally co-localize with the glycosaminoglycans (GAGs) of the basement membrane. GAGs have been shown to accelerate the formation of amyloid fibrils in vitro for a number of protein systems. The high number of data accumulated so far has created the grounds for the construction of a database on the effects of a number of GAGs on different proteins.<h4>Methodology/principal findings</h4>In this study, we have constructed such a database and have used a computational approach that uses a combination of single parameter and multivariate analyses to identify the main chemical factors that determine the GAG-induced acceleration of amyloid formation. We show that the GAG accelerating effect is mainly governed by three parameters that account for three-fourths of the observed experimental variability: the GAG sulfation state, the solute molarity, and the ratio of protein and GAG molar concentrations. We then combined these three parameters into a single equation that predicts, with reasonable accuracy, the acceleration provided by a given GAG in a given condition.<h4>Conclusions/significance</h4>In addition to shedding light on the chemical determinants of the protein:GAG interaction and to providing a novel mathematical predictive tool, our findings highlight the possibility that GAGs may not have such an accelerating effect on protein aggregation under the conditions existing in the basement membrane, given the values of salt molarity and protein:GAG molar ratio existing under such conditions.
format	article
author	Elodie Monsellier Matteo Ramazzotti Niccolò Taddei Fabrizio Chiti
author_facet	Elodie Monsellier Matteo Ramazzotti Niccolò Taddei Fabrizio Chiti
author_sort	Elodie Monsellier
title	A computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.
title_short	A computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.
title_full	A computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.
title_fullStr	A computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.
title_full_unstemmed	A computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.
title_sort	computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/3bb64fc85d6b4834a1577cb347d59b35
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A computational approach for identifying the chemical factors involved in the glycosaminoglycans-mediated acceleration of amyloid fibril formation.

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