Turkish-German University, Molecular Biotechnology, Istanbul, Turkey.
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United States; Laboratory of New Methods in Biology, Institute for Biological Instrumentation, Russian Academy of Sciences, Moscow, Russia.
Prog Mol Biol Transl Sci. 2019;166:145-223. doi: 10.1016/bs.pmbts.2019.05.007. Epub 2019 Jul 19.
Amyloid-β (Aβ) and α-synuclein (αS) are two intrinsically disordered proteins (IDPs) at the centers of the pathogenesis of Alzheimer's and Parkinson's diseases, respectively. Different hypotheses have been proposed for explanation of the molecular mechanisms of the pathogenesis of these two diseases, with these two IDPs being involved in many of these hypotheses. Currently, we do not know, which of these hypothesis is more accurate. Experiments face challenges due to the rapid conformational changes, fast aggregation processes, solvent and paramagnetic effects in studying these two IDPs in detail. Furthermore, pathological modifications impact their structures and energetics. Theoretical studies using computational chemistry and computational biology have been utilized to understand the structures and energetics of Aβ and αS. In this chapter, we introduce Aβ and αS in light of various hypotheses, and discuss different experimental and theoretical techniques that are used to study these two proteins along with their weaknesses and strengths. We suggest that a promising solution for studying Aβ and αS at the center of varying hypotheses could be provided by developing new techniques that link quantum mechanics, statistical mechanics, thermodynamics, bioinformatics to machine learning. Such new developments could also lead to development in experimental techniques.
淀粉样蛋白-β（Aβ）和α-突触核蛋白（αS）分别是阿尔茨海默病和帕金森病发病机制的中心的两种无序蛋白质（IDP）。已经提出了不同的假说来解释这两种疾病发病机制的分子机制，这些假说都涉及到这两种 IDP。目前，我们不知道哪种假说更准确。由于在详细研究这两种 IDP 时涉及到快速构象变化、快速聚集过程、溶剂和顺磁效应，因此实验面临挑战。此外，病理修饰会影响它们的结构和能量。使用计算化学和计算生物学的理论研究已被用于理解 Aβ和αS 的结构和能量。在本章中，我们根据各种假说介绍了 Aβ和αS，并讨论了用于研究这两种蛋白质的不同实验和理论技术及其优缺点。我们建议，通过将量子力学、统计力学、热力学、生物信息学与机器学习联系起来开发新技术，可以为研究处于不同假说中心的 Aβ和αS 提供有前途的解决方案。这些新的发展也可能导致实验技术的发展。
