Comparison of the force fields on monomeric and fibrillar PHF6 of tau protein

The hexapeptide ³⁰⁶VQIVYK³¹¹ (PHF6) plays an important role in the aggregation of Tau protein, which is a hallmark of the Alzheimer's disease (AD). In this article, we systematically compare the effects of eight popular all-atom force fields on the monomeric and fibrillar PHF6 in the molecular dynamics (MD) simulations, which could be helpful in the computer-aided drug design against PHF6. We show that the fibrillar PHF6 prefers β-strand-like structures in all the force fields while the monomer has different structural preferences depending on the force fields. The interactions for stabilizing the fibril are further investigated. In the end, according to the interactions revealed by NMR and the stability of the fibril in the literature, we benchmark the force fields.