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Computational Study on Amyloid Formation and Peptide Self-Assembly

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Authors
박성병
Advisor
신석민
Major
자연과학대학 화학부
Issue Date
2015-08
Publisher
서울대학교 대학원
Keywords
MDα-Synucleinchaperonefacilitator
Description
학위논문 (박사)-- 서울대학교 대학원 : 화학부 물리화학전공, 2015. 8. 신석민.
Abstract
According to the DNA doctrine, a genetic information flows from a DNA to a protein via the processes, such as the replication, the transcription, and the translation. In the post-translation, proteins are folded as corresponded to their functions and at that time self-assembly phenomena take place. On the aspect of the energy landscape, proteins could have the energy-deep corresponding to the folding structure. However, IDPs like α?Synuclein and Aβ40/42 dont show such the energy-deep. Since any faults in the flow of the genetic materials from the replication to the post-translation can cause severe disease, precise understanding on the structure and the dynamics of such proteins would be necessary even for therapeutic purposes.
We performed the MD simulation for several types of α?Synucleins, Aβs, and artificial peptides under various conditions with the REMD and the classical MD methods.
As for α?Synuclein which consists of 140 amino acids and
three functional domains (the membrane binding, the NAC and the acidic domains), P128 in the acidic domain gets in touch with the middle of the NAC domain with higher probabilities and factors, such as the P-to-A mutation in the acidic domain and the change of the acidity, make this characteristics diminished. Therefore, the acidic domain is implied to play a role in the aggregation of α?Synuclein as an intramolecular chaperone.
As for Aβ which is secreted from APP by ß?secretase and has the chain lengths of 40 or 42 in general, the extra IA terminal residues make potential energies of intermediates more discriminated, barriers between intermediates elevated, and gains of binding energies more beneficial. The F(19,20)I/L mutation deepens this characteristics. Therefore, the extra IA residues are thought to play a role in the aggregation of Aβ as a facilitator.
As for artificial peptides which mimic the β-barrel structure in nature, the Coulombic interaction, the hydrogen bonding, the hydrophobic interaction, and the optimally minimized electronic repulsion contribute to the formation of the bionanostructure. Of those interactions, the optimal electronic repulsion is the key factor in controlling the artificials.
Language
English
URI
https://hdl.handle.net/10371/125280
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College of Natural Sciences (자연과학대학)Dept. of Chemistry (화학부)Theses (Ph.D. / Sc.D._화학부)
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