Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations

Abstract The diffusion of protons along biological surfaces and the interaction of biological structures with water are fundamental areas of interest in biology and chemistry. Here, we examine the surface of insulin amyloid fibrils and follow the binding of small molecules (photoacids) that differ a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nadav Amdursky, M. Harunur Rashid, Molly M. Stevens, Irene Yarovsky
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c5801a2a11c94967a4c19ccd1dd07ca0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c5801a2a11c94967a4c19ccd1dd07ca0
record_format	dspace
spelling	oai:doaj.org-article:c5801a2a11c94967a4c19ccd1dd07ca02021-12-02T11:52:37ZExploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations10.1038/s41598-017-06030-42045-2322https://doaj.org/article/c5801a2a11c94967a4c19ccd1dd07ca02017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06030-4https://doaj.org/toc/2045-2322Abstract The diffusion of protons along biological surfaces and the interaction of biological structures with water are fundamental areas of interest in biology and chemistry. Here, we examine the surface of insulin amyloid fibrils and follow the binding of small molecules (photoacids) that differ according to the number and location of their sulfonic groups. We use transient fluorescence combined with a spherically-symmetric diffusion theory to show that the binding mode of different photoacids determines the efficiency of proton dissociation from the photoacid and the dimensionality of the proton’s diffusion. We use molecular dynamics simulations to examine the binding mode and mechanism of the photoacids and its influence on the unique kinetic rates and diffusion properties of the photoacid’s dissociated proton, where we also suggest a proton transfer process between one of the photoacids to proximal histidine residues. We show that the photoacids can be used as fluorescent markers for following the progression of amyloidogenic processes. The detailed characterisation of different binding modes to the surface of amyloid fibrils paves the way for better understanding of the binding mechanism of small molecules to amyloid fibrils.Nadav AmdurskyM. Harunur RashidMolly M. StevensIrene YarovskyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nadav Amdursky M. Harunur Rashid Molly M. Stevens Irene Yarovsky Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations
description	Abstract The diffusion of protons along biological surfaces and the interaction of biological structures with water are fundamental areas of interest in biology and chemistry. Here, we examine the surface of insulin amyloid fibrils and follow the binding of small molecules (photoacids) that differ according to the number and location of their sulfonic groups. We use transient fluorescence combined with a spherically-symmetric diffusion theory to show that the binding mode of different photoacids determines the efficiency of proton dissociation from the photoacid and the dimensionality of the proton’s diffusion. We use molecular dynamics simulations to examine the binding mode and mechanism of the photoacids and its influence on the unique kinetic rates and diffusion properties of the photoacid’s dissociated proton, where we also suggest a proton transfer process between one of the photoacids to proximal histidine residues. We show that the photoacids can be used as fluorescent markers for following the progression of amyloidogenic processes. The detailed characterisation of different binding modes to the surface of amyloid fibrils paves the way for better understanding of the binding mechanism of small molecules to amyloid fibrils.
format	article
author	Nadav Amdursky M. Harunur Rashid Molly M. Stevens Irene Yarovsky
author_facet	Nadav Amdursky M. Harunur Rashid Molly M. Stevens Irene Yarovsky
author_sort	Nadav Amdursky
title	Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations
title_short	Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations
title_full	Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations
title_fullStr	Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations
title_full_unstemmed	Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations
title_sort	exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c5801a2a11c94967a4c19ccd1dd07ca0
work_keys_str_mv	AT nadavamdursky exploringthebindingsitesandprotondiffusiononinsulinamyloidfibrilsurfacesbynaphtholbasedphotoacidfluorescenceandmolecularsimulations AT mharunurrashid exploringthebindingsitesandprotondiffusiononinsulinamyloidfibrilsurfacesbynaphtholbasedphotoacidfluorescenceandmolecularsimulations AT mollymstevens exploringthebindingsitesandprotondiffusiononinsulinamyloidfibrilsurfacesbynaphtholbasedphotoacidfluorescenceandmolecularsimulations AT ireneyarovsky exploringthebindingsitesandprotondiffusiononinsulinamyloidfibrilsurfacesbynaphtholbasedphotoacidfluorescenceandmolecularsimulations
_version_	1718395009618673664

Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations

Ejemplares similares