Investigation of the Structure of Full-Length Tau Proteins with Coarse-Grained and All-Atom Molecular Dynamics Simulations

Tau proteins not only have many important biological
functions
but also are associated with several neurodegenerative diseases, such
as Parkinson’s disease and Alzheimer’s disease (AD).
However, it is still a challenge to identify the atomic structure
of full-length tau proteins due to their lengthy and disordered characteristics
and the factor that there are no crystal structures of full-length
tau proteins available. We performed multi- and large-scale molecular
dynamics simulations of the full-length tau monomer (the 2N4R isoform
and 441 residues) in aqueous solution under biological conditions
with coarse-grained and all-atom force fields. The obtained atomic
structures produced radii of gyration and chemical shifts that are
in excellent agreement with those of experiment. The generated monomer
structure ensemble would be very useful for further studying the oligomerization
mechanism and discovering tau oligomerization inhibitors, which are
important events in AD drug development.