122nd General Meeting of the KCS

Type Poster Presentation
Area Physical Chemistry
Room No. Grand Ballroom
Time 10월 19일 (금요일) 11:00~12:30
Code PHYS.P-221
Subject Computational Study on Structure, Dynamics, and Aggregation of Aβ42 protofibril
Authors MinJun Lee, Jeseong Yoon*, Seokmin Shin*
Department of Chemistry, Seoul National University, Korea
Abstract Amyloid proteins are related to neurodegenerative diseases especially as a main symptom of amyloid fibril deposit in neuronal cell of patients brain. Aβ is known to be the major cause of Alzheimer’s disease. It is suggested that Aβ42 is more toxic than Aβ40. It is possible that the higher toxicity is due to its conformational features. Therefore it is worth to examine the structural features in this viewpoint. Luhrs suggested U-shaped β-arch structure of Aβ42 in 2005, and more recently Xiao succeeded in obtaining high-resolution solid state NMR structure of Aβ42 which is unexpected S-shaped triple-β structure in 2015. Although some experiments provide valuable informations on fibril structure of Aβ42, we need to observe different aspects of structural informations, that is, dynamic and thermodynamic properties of fibril structure as well as its interaction with water in order to explain conformational stability and aggregation mechanism in relation to structure of Aβ42 fibril. We performed molecular dynamics simulations on two different Aβ42 models: U-shaped β-arch and S-shaped triple-β structures. In order to examine both structural stability and aggregation pathway, we performed several different simulation methods which are straightforward extensive simulation, steered molecular dynamics, and replica exchange molecular dynamics (REMD). By analyzing the simulation trajectories, we clarified the structural features of Aβ42 protofibril motif and related them to the stability of fibril. From these results, we tried to interpret the trajectories of pulling simulation and REMD and predict aggregation pathway of Aβ42 fibril.
E-mail ak3220@snu.ac.kr