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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Michał Koliński, Robert Dec, Wojciech Dzwolak
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
Acceso en línea:https://doaj.org/article/879d45cd70bd4f599a385c086bf1f607
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:879d45cd70bd4f599a385c086bf1f607
record_format dspace
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
_version_ 1718411814399639552