Exploring Intra- and Inter-Regional Interactions in the IDP α-Synuclein Using smFRET and MD Simulations.

Theoretical concepts from polymer physics are often used to describe intrinsically disordered proteins (IDPs). However, amino acid interactions within and between regions of the protein can lead to deviations from typical polymer scaling behavior and even to short-lived secondary structures. To investigate the key interactions in the dynamic IDP α-synuclein (αS) at the amino acid level, we conducted single-molecule fluorescence resonance energy transfer (smFRET) experiments and coarse-grained molecular dynamics (CG-MD) simulations.