期刊
ACS CHEMICAL NEUROSCIENCE
卷 4, 期 11, 页码 1446-1457出版社
AMER CHEMICAL SOC
DOI: 10.1021/cn400110d
关键词
Amyloid simulation; Alzheimer's disease; amyloid-beta proteins; molecular dynamics; D7N mutation; monomer; dimer
资金
- Narodowe Centrum Nauki in Poland [2011/01/B/NZ1/01622]
- Department of Science and Technology at Ho Chi Minh City, Vietnam
- ANR [12-BS07-0017-01]
- Cooperation between CNRS/Polish Science Academy/Poland
Recent experiments have shown that the mutation Tottori (D7N) alters the toxicity, assembly and rate of fibril formation of the wild type (WT) amyloid beta (A beta) A beta(40) and A beta(42) peptides. We used all-atom molecular dynamics simulations in explicit solvent of the monomer and dimer of both alloforms with their WT and D7N sequences. The monomer simulations starting from a random coil and totaling 3 mu s show that the D7N mutation changes the fold and the network of salt bridges in both alloforms. The dimer simulations starting from the amyloid fibrillar states and totaling 4.4 mu s also reveal noticeable changes in terms of secondary structure, salt bridge, and topology. Overall, this study provides physical insights into the enhanced rate of fibril formation upon D7N mutation and an atomic picture of the D7N-mediated conformational change on A beta(40) and A beta(42) peptides.
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