Molecular Dynamics Simulations of the Salt Effect on Amyloid Beta Peptide (Aβ14-23) Aggregation Process

• Main Authors: Hong-Ming Chen, 陳泓銘
• Other Authors: Sheh-Yi Sheu
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/83594946747082938386

碩士 === 國立陽明大學 === 生物醫學資訊研究所 === 101 === Alzheimer’s disease (AD) is a neurodegenerative disease, and this disease causes senile dementia. AD has an important pathological feature that neurons are surrounded by senile plaques in brain. Senile plaques (SP) are constructed by the aggregation of amyloid β-peptide (Aβ). Besides, the researchers discovered that the aggregation type of Aβ possesses has neurotoxicity. Aβ mutation or environmental factor can affect the aggregation process of Aβ. Therefore, we studied the different effects on the aggregation of Aβ by molecular dynamics simulation. In previous research, different mutant types can have different effect on the aggregation of Aβ. Mutant type A21G (Flemish) and L17A/F19A can reduce the aggregation of Aβ; mutant type E22K (Italian) and D23N (Iowa) can increase the aggregation of Aβ. The ionic strength or pH value of solution also can affect the aggregation of Aβ. If Aβ is in physiological ionic strength solution or acidic environment, the aggregation of Aβ will be faster and more stable. Because Aβ14-23 is the shortest sequence can form senile plaques, we have chosen Aβ14-23 dimer as our model to study the mechanism of Aβ aggregation. Different types of Aβ have been studied including wild type, L17A/F19A, A21G, E22K and D23N. About the environment as factor, we have performed molecular dynamics simulation in various ionic strength solution and acidic solution. According to the results, we found that the effect of ionic strength on Aβ(E22K) and Aβ(D23N) are not obvious, only the β-sheet formation is faster; in contrast, for Aβ(wild type), Aβ(A21G) and Aβ(L17A/F19A) the β-sheets, formation rate and stability were increased. The acidic solution caused the aggregation of the solution wild type and every mutant type to be more favor than neutral; besides, ionic strength effect has weaker influence in acidic solution. Furthermore, the acidic effect enhances van der Waals interaction and electrostatic interaction, and then causes the aggregation of Aβ. For all the systems, the conformational entropy changes are similar, but the enthalpy changes are distinct. It showed that the main factor which could affect the Aβ aggregation is the variation of Aβ residues.