Molecular Dynamics Studies of Tau Monomer and Dimer Conformations

Abstract

The microtubule associated protein tau is important in nucleating and maintain microtubule spacing and structure in neuronal axons. Over-phosphorylated tau is implicated in Alzheimer's disease, where it is found in plaques. Tau likely forms dimers as there is only one microtubule binding domain per tau. Because tau in an intrinsically disordered protein, conventional modeling techniques are not sufficient to accurately describe its structure. In order to simulate tau, we therefore must generate many starting structures in order to form a more complete ensemble. We present preliminary molecular dynamics studies for the n-terminal half of the tau monomer and dimer models (residues 1-241) for tau's normal function as a microtubule spacer and adduce the distributions of end-to-end separations. Because normal tau has several phosphorylation sites, we also investigate how varying phosphorylation locations on the n-terminal half of tau affect its structure.Supported by US NSF Grant DMR 1207624.