Finding the transition state of α-synuclein in α-β transition
Paper ID : 1155-ICNS
Anahita Khammari1, Shahriar Arab1, Mohammad Reza Ejtehadi *2
1Department of Biophysics, School of Biological sciences, Tarbiat Modares University, Tehran, Iran
2Department pf Physics, Sharif University of Technology
Amyloid fibrillation of alpha-synuclein (αS) is implicated in a several of neurological diseases including Parkinson’s disease. To create amyloid fibrils, there is a need for a monomeric structural transition from helix to extended states in αS, followed by the creating of beta-sheets, and eventually the forming of amyloid fibrils. The alpha-helix to beta-sheet transition (αβT) is a deformation mechanism in the helix-rich proteins that speeds up the formation of amyloid fibrils. In this study, based on the sequence and structural information of αS protein, the most important regions are identified that act as the initiating nuclei and created unstable intermediate structures in the αβT process. In this regard, targeted molecular dynamics simulations is performed in explicit solvent models at physiological conditions. The results four intermediate structures are found which one of them was introduced as a transition state (TS). The goal of this project, studying the important intermediate structures and finding the transition state during αβT, may be useful in the better understanding of the amyloid fibril formation mechanism.
α-synuclein; Targeted molecular dynamics; α-β conformational transition; Transition state
Status : Abstract Accepted (Poster Presentation)