The impacts of solvation and segment variations on the structures of amyloid-beta

Date
2011
Authors
Kitahara, Taizo
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Abstract

Amyloid-beta (Abeta) is a disordered peptide and is at the center of cerebral amyloid angiopathy and Alzheimer's disease. Currently, the impacts of solvation and segment variation on the structures of Abeta are poorly understood. A large amount of human body consists of water and solvation effects can influence the disordered peptide structure. Furthermore, segment variations including different fragment sizes and mutation have been related to Alzheimer's disease. We performed molecular dynamics simulations coupled with thermodynamic calculations and special sampling techniques to elucidate the impacts of solvation and segment variations on Abeta structures. Various smaller fragment sizes of Abeta have been utilized to mimic the properties of the full-length Abeta peptide. Among these, the widely used smaller fragment peptides are Abeta16 and Abeta28. Our studies show that the Asp1-Lys16 and Asp1-Asp28 regions of the full length Abeta42 peptide cannot be completely mimicked by studying the Abeta16 and Abeta28 peptides in an aqueous solution environment. Our studies indicate that Arg5 plays significant roles in the intra-molecular interactions of the wild type Abeta peptide. The mutation of Arg with Ala impacts the structures of the wild-type peptide. Even though the secondary and tertiary structure properties of the R5A mutant are different from those of wild type Abeta42 peptides in aqueous medium, the conformational Gibbs free energies are similar. The results provide the lacking knowledge of the impacts of solvation and segment variations on the structures of Abeta at atomic level with dynamics and can be useful for the fundamental understanding of the properties of Abeta and for designing more efficient treatments for Alzheimer's disease.

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Keywords
, Abeta, AMYLOID-β, Amyloid-beta, Arg, fragment, solvation
Citation
Department
Chemistry