Use Monte Carlo Method to Study the Formation of Amyloid Beta Fibril in Silico

• Main Authors: Cheng-Yu Ma, 馬誠佑
• Other Authors: Sheh-Yi Sheu
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/63861523042761723648

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.