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Article

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

1
Bioinformatics Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego St., 02-106 Warsaw, Poland
2
Faculty of Chemistry, Biological and Chemical Research Center, University of Warsaw, 1 Pasteura St., 02-093 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Yifat Miller
Int. J. Mol. Sci. 2021, 22(22), 12325; https://doi.org/10.3390/ijms222212325
Received: 14 October 2021 / Revised: 8 November 2021 / Accepted: 12 November 2021 / Published: 15 November 2021
(This article belongs to the Special Issue Advanced Research of Amyloids)
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 ACC1-13 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 ACC1-13 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. View Full-Text
Keywords: multiscale modeling; amyloid fibril; flexible docking; fibril structure prediction; peptide aggregation; molecular dynamics; peptide docking; protofilament structure; CABS-dock multiscale modeling; amyloid fibril; flexible docking; fibril structure prediction; peptide aggregation; molecular dynamics; peptide docking; protofilament structure; CABS-dock
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MDPI and ACS Style

Koliński, M.; Dec, R.; Dzwolak, W. Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin. Int. J. Mol. Sci. 2021, 22, 12325. https://doi.org/10.3390/ijms222212325

AMA Style

Koliński M, Dec R, Dzwolak W. Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin. International Journal of Molecular Sciences. 2021; 22(22):12325. https://doi.org/10.3390/ijms222212325

Chicago/Turabian Style

Koliński, Michał, Robert Dec, and Wojciech Dzwolak. 2021. "Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin" International Journal of Molecular Sciences 22, no. 22: 12325. https://doi.org/10.3390/ijms222212325

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