In Silico Binding Mode Proposed for Flavonoid Ligands of Tau Protein with Interest in Alzheimer's Disease
Carlos Henrique Tomich de Paula da Silva,
Vinicius Barreto da Silva.
An intracellular hallmark of Alzheimer’s Disease (AD) is accumulation of hyperphosphorylated tau as paired
helical filaments (PHF). A significant advance in understanding the behavior of tau occurred when it was reported that
VQIVYK hexapeptide motif is responsible for initiating the process of aggregation. In the last years, a great number of
Tau aggregation inhibitors have been developed, including flavonoids. However, the binding mode of these potential
drugs is not well established. In this work, the behavior and conformational stability of the Tau hexapeptide306VQIVYK311
were investigated in the presence of two known flavonoid inhibitors using Molecular Interaction Fields (MIFs), pharmacophore
perception and molecular dynamics (MD) simulations. We have also proposed a likely binding mode for such inhibitors
with the hexapeptide, which agrees with experimental data and is able to explain structure-activity relationships
between different flavonoids.
Keywords: Alzheimer’s disease, tau protein, flavonoids, molecular interaction fields, pharmacophore perception, molecular
Rights & PermissionsPrintExport