FIGURE 1.

VQIK(Ac)YKP peptides dock to VQIVYK. Experimental peptides docked in parallel to the superior portion of PDB 5o3l 2N4R PHF (A–C) demonstrate preferential binding to ³⁰⁶VQIVYK³¹¹, whereas experimental peptides docked to PDB 6QJH 2N4R Tau snake filament (D–E) bind to both ³⁰⁶VQIVYK³¹¹ and ²⁷⁵VQIINK²⁸⁰. (A) Ac‐VQIVYK‐NH2; (B) AC‐VQIK(Ac)YK‐NH2; (C) Ac‐VQIK(Ac)YKP‐NH2, notice the peptide extending to interact with the parallel β‐sheet of ³⁰⁶VQIVYK³¹¹. (D) Ac‐VQIVYK‐NH2 binding in parallel to the filament; (E) Ac‐VQIK(Ac)YKP‐NH2 binding in anti‐parallel to the filament at ³⁰⁶VQIVYK³¹¹ position, and in parallel at the ²⁷⁵VQIINK²⁸⁰ position. (F) Summary table of the highest computationally calculated energy values describing the docked compounds to PDB‐5o3l and PDB‐5QJH (emphasis on VQIINK). Lower scores indicate more powerful interactions. ICM score of <–32 indicates a strong binding.