The tau protein belongs to the category of Intrinsically Disordered Proteins (IDPs), which in their native state do not have an average stable structure and fluctuate between many conformations. In its physiological state, tau helps nucleating and stabilizing the microtubules in the axons of the neurons. On the other hand, the same tau is involved in the development of the Alzheimer disease, when it aggregates in paired helical filaments (PHFs) forming fibrils, which form insoluble tangles. The beginning of the pathological aggregation of tau has been attributed to a local transition of protein portions from random coil to a beta-sheet. These structures would very likely be transient; therefore, we performed a Molecular Dynamics simulation of tau to gather information on the existence of segments of tau endowed with a secondary structure. We combined the results of our simulation with small-angle X-ray scattering experimental data to extract from the dynamics a set of most probable conformations of tau. The analysis of these conformations highlights the presence of transient secondary structures like turns, beta-bridges, beta-sheets, and alpha-helices. It also shows that a large segment of the N-terminal region is found near the repeats domain, in a globular-like shape.
