COMPARATIVE STABILITY ANALYSIS OF D23N MUTATED Aβ

• Published in: T.A.S.K. quarterly Vol. 18; no. 4
• Main Authors: ERIK J. ALRED, EMILY G. SCHEELE, WORKALEMAHU M. BERHANU, ULRICH H. E. HANSMANN
• Format: Journal Article
• Language: English
• Published: Gdańsk University of Technology 01-10-2014
• Subjects: Iowa mutant; molecular dynamics; parallel and antiparallel β sheets; structural polymorphism
• ISSN: 1428-6394
• DOI: 10.17466/TQ2014/18.4/N

Amyloid β (Aβ) is the subject of numerous studies due to its link to the devastating Alzheimer’s disease and it exists in a parallel structure in fibril aggregate. The Iowa mutant (D23N) Aβ posses a unique antiparallel fibril aggregate structure and can also form parallel structure. This structural difference, coupled with the fact that occurrence of the Iowa mutant is correlated with early onset Alzheimer’s, suggests to use these peptides as candidates for computational studies of the structural determinants of the toxicity of Alzheimer’s disease. In order to compare the two observed Aβ structural motifs, we designed a computational study to probe the factors that affect the stability of parallel and antiparallel aggregates. Since the structural changes may occur on a timescale beyond that sampled in traditional molecular dynamics (MD), we employed a techniques of scaling the mass to reduce the solution’s viscosity and compared the results to regular molecular dynamics. The knowledge gained from this study could provide insight into the mechanism of selection for antiparallel and parallel two fold structures.