Document Detail

Side-chain hydrophobicity and the stability of Aβ₁₆₋₂₂ aggregates.
MedLine Citation:
PMID:  23015407     Owner:  NLM     Status:  MEDLINE    
Recent mutagenesis studies using the hydrophobic segment of Aβ suggest that aromatic π-stacking interactions may not be critical for fibril formation. We have tested this conjecture by probing the effect of Leu, Ile, and Ala mutation of the aromatic Phe residues at positions 19 and 20, on the double-layer hexametric chains of Aβ fragment Aβ₁₆₋₂₂ using explicit solvent all-atom molecular dynamics. As these simulations rely on the accuracy of the utilized force fields, we first evaluated the dynamic and stability dependence on various force fields of small amyloid aggregates. These initial investigations led us to choose AMBER99SB-ILDN as force field in multiple long molecular dynamics simulations of 100 ns that probe the stability of the wild-type and mutants oligomers. Single-point and double-point mutants confirm that size and hydrophobicity are key for the aggregation and stability of the hydrophobic core region (Aβ₁₆₋₂₂). This suggests as a venue for designing Aβ aggregation inhibitors the substitution of residues (especially, Phe 19 and 20) in the hydrophobic region (Aβ₁₆₋₂₂) with natural and non-natural amino acids of similar size and hydrophobicity.
Workalemahu M Berhanu; Ulrich H E Hansmann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Protein science : a publication of the Protein Society     Volume:  21     ISSN:  1469-896X     ISO Abbreviation:  Protein Sci.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-27     Completed Date:  2013-04-29     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  9211750     Medline TA:  Protein Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1837-48     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 The Protein Society.
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MeSH Terms
Amino Acid Sequence
Amyloid beta-Peptides / chemistry*,  genetics*
Hydrophobic and Hydrophilic Interactions
Molecular Dynamics Simulation
Molecular Sequence Data
Peptide Fragments / chemistry*,  genetics*
Point Mutation
Protein Stability
Grant Support
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Peptide Fragments

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