Einstein Model of a Graph to Characterize Protein Folded/Unfolded States.

The folded structures of proteins can be accurately predicted by deep learning algorithms from their amino-acid sequences. By contrast, in spite of decades of research studies, the prediction of folding pathways and the unfolded and misfolded states of proteins, which are intimately related to diseases, remains challenging. A two-state (folded/unfolded) description of protein folding dynamics hides the complexity of the unfolded and misfolded microstates.

Wild-Type -Synuclein and Variants Occur in Different Disordered Dimers and Pre-Fibrillar Conformations in Early Stage of Aggregation.

-Synuclein is a 140 amino-acid intrinsically disordered protein mainly found in the brain. Toxic -synuclein aggregates are the molecular hallmarks of Parkinson's disease. studies showed that -synuclein aggregates in oligomeric structures of several 10th of monomers and into cylindrical structures (fibrils), comprising hundred to thousands of proteins, with polymorphic cross--sheet conformations.

Missense Mutations Modify the Conformational Ensemble of the -Synuclein Monomer Which Exhibits a Two-Phase Characteristic.

-Synuclein is an intrinsically disordered protein occurring in different conformations and prone to aggregate in -sheet structures, which are the hallmark of the Parkinson disease. Missense mutations are associated with familial forms of this neuropathy. How these single amino-acid substitutions modify the conformations of wild-type -synuclein is unclear.