Fig. 6: Thermodynamic analysis of tau fibril polymorphs.

a Mapping the positions of identified aggregation motifs on tau fibrils polymorphs of major structural classes. b, c Heatmap plot indicating the per residue energy contributions for structurally determined tau amyloid fibril cores derived from different patient extracts or fibrils produced in vitro⁴⁵. PDB IDs of individual tau fibril structures are shown on the Y-axis, separated by dashed lines based on disease type, whereas the X-axis indicates tau residue numbers. The top panel bar plot (b) indicates the sum of energy contributions per residue for all structures shown in the heatmap, with the identified aggregation motif regions shown in shaded boxes and coloured as in a. d–h Tau fibril polymorphs are stabilised primarily by the identified aggregation motifs. Residue sidechains are shown in ball representation, with important aggregation motif interactions highlighted and the rest of the residue sidechains faded out. Residues are coloured based on the calculated energies shown in c.