Medicine and Health Sciences Commons^™

Insights Into The Molecular Mechanisms Of Alzheimer’S And Parkinson’S Diseases With Molecular Simulations: Understanding The Roles Of Artificial And Pathological Missense Mutations In Intrinsically Disordered Proteins Related To Pathology, Orkid Coskuner-Weber, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Amyloid-β and α-synuclein are intrinsically disordered proteins (IDPs), which are at the center of Alzheimer’s and Parkinson’s disease pathologies, respectively. These IDPs are extremely flexible and do not adopt stable structures. Furthermore, both amyloid-β and α-synuclein can form toxic oligomers, amyloid fibrils and other type of aggregates in Alzheimer’s and Parkinson’s diseases. Experimentalists face challenges in investigating the structures and thermodynamic properties of these IDPs in their monomeric and oligomeric forms due to the rapid conformational changes, fast aggregation processes and strong solvent effects. Classical molecular dynamics simulations complement experiments and provide structural information at the atomic level with dynamics …