INVESTIGADORES
ENRIZENRIZ] ricardoricardo] danieldaniel]
artículos
Título:
Model peptides for Binding Studies on peptide-peptide Interactions: The Case of Amyloid beta (1-42) Aggregates
Autor/es:
M.F.MASMAN, U. M. EISEL, I. CSIZMADIA, B. VISKOLZ, R.D.ENRIZENRIZ], B. PENKE, P. G.M. LUITE
Revista:
JOURNAL OF PHYSICAL CHEMISTRY B
Editorial:
Am. Chem Soc
Referencias:
Lugar: Washington; Año: 2009 vol. 113 p. 11710 - 11710
ISSN:
1089-5647
Resumen:
Amyloid oligomers are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases including Alzheimer’s disease. Using MD simulation techniques, we explored the contributions of the different structural elements of trimeric and pentameric full-length A1-42 aggregates in solution to their stability and conformational dynamics. We found that our models are stable at a temperature of 310 K, andconverge toward an interdigitated side-chain packing for intermolecular contacts within the two -sheet regions of the aggregates: 1 (residues 18-26) and 2 (residues 31-42). MD simulations reveal that the -strand twist is a characteristic element of A-aggregates, permitting a compact, interdigitated packing of side chains from neighboring -sheets. The 2 portion formed a tightly organized -helix, whereas the 1 portion did not show such a firm structural organization, although it maintained its -sheet conformation. Our simulations indicate that the hydrophobic core comprising the 2 portion of the aggregate is a crucial stabilizing element in the A aggregation process. On the basis of these structure-stability findings, the 2 portion emerges as an optimal target for further antiamyloid drug design.1-42 aggregates in solution to their stability and conformational dynamics. We found that our models are stable at a temperature of 310 K, and converge toward an interdigitated side-chain packing for intermolecular contacts within the two -sheet regions of the aggregates: 1 (residues 18-26) and 2 (residues 31-42). MD simulations reveal that the -strand twist is a characteristic element of A-aggregates, permitting a compact, interdigitated packing of side chains from neighboring beta-sheets. The 2 portion formed a tightly organized -helix, whereas the 1 portion did not show such a firm structural organization, although it maintained its -sheet conformation. Our simulations indicate that the hydrophobic core comprising the 2 portion of the aggregate is a crucial stabilizing element
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