Polarization of Intrinsically Disordered Proteins in the Presence of Charged Biopolymers: the Case of Tau Protein

Tau protein is an intrinsically disordered protein known to be associated with the progression of neurodegenerative diseases. In cells, tau interacts with charged macromolecules, including high charge density polyanions such as RNA and microtubules. Although attraction between tau protein and negatively charged biopolymers is thought to play an important role in cell function, the mechanisms leading to attraction between tau protein and negatively charged biopolymers remain poorly understood. We study tau protein conformations and polarization using molecular dynamics simulations. First, we study the electrostatically driven collapse of tau protein, and connect the resulting conformation to features of its charge sequence. We then study how the conformations of tau protein change in the presence of a constant electric field and in the presence of a negatively charged biopolymer. With the latter, we quantify polarization induced attraction of tau protein to biopolymers. The implications of conformational changes of tau protein as it interacts with polyanions inside the cell will be discussed.