Hyperphosphorylation of the Tau protein is a key molecular event in Alzheimer's disease and related Tauopathies, leading to loss of microtubule-binding function, misfolding, and aggregation into neurofibrillary tangles. More than 95% of Tau consists of intrinsically disordered regions (IDRs), making traditional structure-determination techniques such as X-ray crystallography or cryo-EM unsuitable for obtaining high-resolution conformational information. This lack of structural data represents a fundamental barrier to rational design of small molecules targeting pathological forms of Tau. We propose to investigate the conformational ensemble of hyperphosphorylated Tau using Replica Exchange Molecular Dynamics (REMD) simulations. REMD is a powerful enhanced-sampling technique that can overcome energetic barriers and provide an accurate representation of the structural and thermodynamic landscape of highly flexible and disordered systems. By generating an atomistic ensemble of hyperphosphorylated Tau, we aim to characterize changes in disorder, transient secondary structure, and long-range intramolecular contacts induced by multisite phosphorylation. The resulting ensemble will provide a foundation for structure-based drug design targeting pathological Tau species (pTau) and fill a current gap in experimental structural data.