Structures of the intrinsically disordered A beta, tau and alpha-synuclein proteins in aqueous solution from computer simulations

摘要

Intrinsically disordered proteins (IDPs) play many biological roles in the human proteome ranging from vesicular transport, signal transduction to neurodegenerative diseases. The A beta and tau proteins, and the alpha-synuclein protein, key players in Alzheimer's and Parkinson's diseases, respectively are fully disordered at the monomer level. The structural heterogeneity of the monomeric and oligomeric states and the high self-assembly propensity of these three IDPs have precluded experimental structural determination. Simulations have been used to determine the atomic structures of these IDPs. In this article, we review recent computer models to capture the equilibrium ensemble of A beta, tau and alpha-synuclein proteins at different association steps in aqueous solution and present new results of the PEP-FOLD framework on alpha-synuclein monomer.