Oligomer formation of amyloid-beta studied by new constant pH simulations

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18531
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biophysics
• Research Institution: Institute for Molecular Science
• Principal Investigator: Itoh Satoru 分子科学研究所, 理論・計算分子科学研究領域, 助教 (90595381)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アミロイド線維 / 分子シミュレーション

Outline of Final Research Achievements

The oligomer formation process of Abeta(29-42), which is a fragment of the amyloid beta (Abeta) peptide, was studied by Coulomb replica-permutation molecular dynamics simulations. It was found that an oligomer increased in size by addition of a monomer to the oligomer sequentially.
We also performed Coulomb replica-permutation molecular dynamics simulations to clarify the dimer formation process of the full-length Abeta peptides. As a result, it was found that the intramolecular beta-sheet structure accelerated the formation of an intermolecular beta-sheet structure.

Free Research Field

生物物理

Academic Significance and Societal Importance of the Research Achievements

アミロイドベータペプチド(Abeta)が形成するオリゴマーはアルツハイマー病との関連が指摘されており、アルツハイマー病を克服するためにはオリゴマー形成過程の解明は不可欠である。本研究によりAbetaのオリゴマー形成初期過程を原子レベルで明らかにした。本研究を発展させることでアルツハイマー病の治療薬開発に貢献できると考える。