Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation
Amyloid fibrils are found in many fatal neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, type II diabetes, and prion disease. The VEALYL short peptide from insulin has been confirmed to aggregate amyloid-like fibrils. However, the aggregation mechanism of amyloi...
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| Format: | Online |
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Public Library of Science
2012
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349666/ |
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pubmed-3349666 |
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pubmed-33496662012-05-15 Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation Ye, Wei Chen, Yue Wang, Wei Yu, Qingfen Li, Yixue Zhang, Jian Chen, Hai-Feng Research Article Amyloid fibrils are found in many fatal neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, type II diabetes, and prion disease. The VEALYL short peptide from insulin has been confirmed to aggregate amyloid-like fibrils. However, the aggregation mechanism of amyloid fibril is poorly understood. Here, we utilized molecular dynamics simulation to analyse the stability of VEALYL hexamer. The statistical results indicate that hydrophobic residues play key roles in stabilizing VEALYL hexamer. Single point and two linkage mutants confirmed that Val1, Leu4, and Tyr5 of VEALYL are key residues. The consistency of the results for the VEALYL oligomer suggests that the intermediate states might be trimer (3-0) and pentamer(3-2). These results can help us to obtain an insight into the aggregation mechanism of amyloid fibril. These methods can be used to study the stability of amyloid fibril from other short peptides. Public Library of Science 2012-05-10 /pmc/articles/PMC3349666/ /pubmed/22590535 http://dx.doi.org/10.1371/journal.pone.0036382 Text en Ye et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Ye, Wei Chen, Yue Wang, Wei Yu, Qingfen Li, Yixue Zhang, Jian Chen, Hai-Feng |
| spellingShingle |
Ye, Wei Chen, Yue Wang, Wei Yu, Qingfen Li, Yixue Zhang, Jian Chen, Hai-Feng Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation |
| author_facet |
Ye, Wei Chen, Yue Wang, Wei Yu, Qingfen Li, Yixue Zhang, Jian Chen, Hai-Feng |
| author_sort |
Ye, Wei |
| title |
Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation |
| title_short |
Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation |
| title_full |
Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation |
| title_fullStr |
Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation |
| title_full_unstemmed |
Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation |
| title_sort |
insight into the stability of cross-β amyloid fibril from vealyl short peptide with molecular dynamics simulation |
| description |
Amyloid fibrils are found in many fatal neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, type II diabetes, and prion disease. The VEALYL short peptide from insulin has been confirmed to aggregate amyloid-like fibrils. However, the aggregation mechanism of amyloid fibril is poorly understood. Here, we utilized molecular dynamics simulation to analyse the stability of VEALYL hexamer. The statistical results indicate that hydrophobic residues play key roles in stabilizing VEALYL hexamer. Single point and two linkage mutants confirmed that Val1, Leu4, and Tyr5 of VEALYL are key residues. The consistency of the results for the VEALYL oligomer suggests that the intermediate states might be trimer (3-0) and pentamer(3-2). These results can help us to obtain an insight into the aggregation mechanism of amyloid fibril. These methods can be used to study the stability of amyloid fibril from other short peptides. |
| publisher |
Public Library of Science |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349666/ |
| _version_ |
1611528792526815232 |