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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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) |
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DOAJ |
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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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1718411814399639552 |