Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin

Computational prediction of molecular structures of amyloid fibrils remains an exceedingly challenging task. In this work, we propose a multi-scale modeling procedure for the structure prediction of amyloid fibrils formed by the association of ACC<sub>1-13</sub> aggregation-prone peptide...

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Autores principales:	Michał Koliński, Robert Dec, Wojciech Dzwolak
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	multiscale modeling amyloid fibril flexible docking fibril structure prediction peptide aggregation molecular dynamics Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/879d45cd70bd4f599a385c086bf1f607
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spelling	oai:doaj.org-article:879d45cd70bd4f599a385c086bf1f6072021-11-25T17:55:29ZMultiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin10.3390/ijms2222123251422-00671661-6596https://doaj.org/article/879d45cd70bd4f599a385c086bf1f6072021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12325https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Computational prediction of molecular structures of amyloid fibrils remains an exceedingly challenging task. In this work, we propose a multi-scale modeling procedure for the structure prediction of amyloid fibrils formed by the association of ACC<sub>1-13</sub> aggregation-prone peptides derived from the N-terminal region of insulin’s A-chain. First, a large number of protofilament models composed of five copies of interacting ACC<sub>1-13</sub> peptides were predicted by application of CABS-dock coarse-grained (CG) docking simulations. Next, the models were reconstructed to all-atom (AA) representations and refined during molecular dynamics (MD) simulations in explicit solvent. The top-scored protofilament models, selected using symmetry criteria, were used for the assembly of long fibril structures. Finally, the amyloid fibril models resulting from the AA MD simulations were compared with atomic force microscopy (AFM) imaging experimental data. The obtained results indicate that the proposed multi-scale modeling procedure is capable of predicting protofilaments with high accuracy and may be applied for structure prediction and analysis of other amyloid fibrils.Michał KolińskiRobert DecWojciech DzwolakMDPI AGarticlemultiscale modelingamyloid fibrilflexible dockingfibril structure predictionpeptide aggregationmolecular dynamicsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12325, p 12325 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	multiscale modeling amyloid fibril flexible docking fibril structure prediction peptide aggregation molecular dynamics Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	multiscale modeling amyloid fibril flexible docking fibril structure prediction peptide aggregation molecular dynamics Biology (General) QH301-705.5 Chemistry QD1-999 Michał Koliński Robert Dec Wojciech Dzwolak Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin
description	Computational prediction of molecular structures of amyloid fibrils remains an exceedingly challenging task. In this work, we propose a multi-scale modeling procedure for the structure prediction of amyloid fibrils formed by the association of ACC<sub>1-13</sub> aggregation-prone peptides derived from the N-terminal region of insulin’s A-chain. First, a large number of protofilament models composed of five copies of interacting ACC<sub>1-13</sub> peptides were predicted by application of CABS-dock coarse-grained (CG) docking simulations. Next, the models were reconstructed to all-atom (AA) representations and refined during molecular dynamics (MD) simulations in explicit solvent. The top-scored protofilament models, selected using symmetry criteria, were used for the assembly of long fibril structures. Finally, the amyloid fibril models resulting from the AA MD simulations were compared with atomic force microscopy (AFM) imaging experimental data. The obtained results indicate that the proposed multi-scale modeling procedure is capable of predicting protofilaments with high accuracy and may be applied for structure prediction and analysis of other amyloid fibrils.
format	article
author	Michał Koliński Robert Dec Wojciech Dzwolak
author_facet	Michał Koliński Robert Dec Wojciech Dzwolak
author_sort	Michał Koliński
title	Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin
title_short	Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin
title_full	Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin
title_fullStr	Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin
title_full_unstemmed	Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin
title_sort	multiscale modeling of amyloid fibrils formed by aggregating peptides derived from the amyloidogenic fragment of the a-chain of insulin
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/879d45cd70bd4f599a385c086bf1f607
work_keys_str_mv	AT michałkolinski multiscalemodelingofamyloidfibrilsformedbyaggregatingpeptidesderivedfromtheamyloidogenicfragmentoftheachainofinsulin AT robertdec multiscalemodelingofamyloidfibrilsformedbyaggregatingpeptidesderivedfromtheamyloidogenicfragmentoftheachainofinsulin AT wojciechdzwolak multiscalemodelingofamyloidfibrilsformedbyaggregatingpeptidesderivedfromtheamyloidogenicfragmentoftheachainofinsulin
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Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin

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