Predicting the location of the non-local contacts in α-synuclein

In this paper, the Sequential Collapse Model (SCM) for protein folding pathways is applied to investigate the location of the non-local contacts in the intrinsically disordered state of α-synuclein, a protein implicated in the onset and spreading of several serious neurodegenerative diseases. The model relies on the entropic cost of forming protein loops due to self-crowding effects, and the protein sequence to determine contact location and stability. It is found that the model predicts the existence of several possible non-local contacts, and the location of the non-local contacts is consistent with existing experimental evidence. The bearing of these findings on the pathogenic mechanism and its regulation is discussed. •A simple model of contact formation is applied to predict the location of the non-local contacts in α-synuclein.•The predicted non-local contacts correlate well with existing experimental evidence.•The role of the non-local contacts in the oligomerization process is discussed.•Directions for future research focused on the predicted non-local contacts are discussed.