Domain focused and residue focused phosphorylation effect on tau protein: A molecular dynamics simulation study

Phosphorylation has been hypothesized to alter the ability of tau protein bind with microtubules (MT), and pathological level phosphorylation can incorporate formation Paired Helical Filaments (PHF) in affected tau. Study effect on different domains (projection domain, microtubule binding sites N-terminus tail) is important obtain insight about neuropathology. In an earlier study, we have already obtained mechanical properties behavior single dimerized observed tau-MT interaction for normal phosphorylation. This study attempts insights tau, using molecular dynamics (MD) simulation aid CHARMM force field under high strain rate. It also determines residue focused accumulation tendency. The results show that protein, unfolding stiffness does not differ significantly due phosphorylation, but stretching be much higher than normally phosphorylated protein. For required separate forming dimer similar individual less case all domains. simulations, it found separation from MT occurs at projection domain tail, altogether state. shows separates stronger tendency state, while preserving highly stretchable flexible characteristic provides mechanochemical phenomena relevant traumatic brain injury (TBI) scenario, where result loading posttranslational modification as well conformation decides behavior.