| Summary: | 碩士 === 國立陽明大學 === 生物醫學資訊研究所 === 96 === Alzheimer’s disease (AD) is an irreversibly degenerative neuron disease and senile
plaques can be found in the region whose function is about memory and cognition in
brain tissue. The cause of Alzheimer’s disease is not well-understood nowadays but
previous research indicates that the disease is associated with senile plaques in the
brain. Senile plaques are made up of small peptides, 39 to 43 amino acids in length,
called beta-amyloid (also written as Aβ). Aβ is an α-helix transmembrane protein, but
when many Aβs aggregate to form amyloid fibrils, Aβ forms two β-strands in
secondary structure instead of α-helices and also forms a β-sheet with others up and
down. Further understanding the cause and mechanism of the formation of amyloid
fibrils will be helpful in drug design and therapy development of AD. Previous
research indicates that if the residues in Aβ15-23 and Aβ12-26 are replaced with
prolines, Aβ cannot aggregate into amyloid fibrils. Therefore Aβ15-23 is used as a
target in this research. A 3D model of Aβ15-23 was built, using Monte Carlo
simulation to form amyloid fibrils and the binding free energy of the aggregation
progress in silico was calculated to figure out the bottle-neck step and pathway of
amyloid fibril formation. We found that the formation of hexamers in parallel β-sheet
conformation and dimers, tetramers, nonamers in anti-parallel β-sheet conformation
may be the critical step in the aggregation of Aβ15-23.
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