MAPT and Alzheimer disease: For the first time, we systematically studiedthe pathological impact of the phosphorylation on MT binding and conformationof tau repeat R2 using the state of the art of all-atom MD simulations.Considering the vital role of the repeat R2 on MT binding and aggregationof full-length tau proteins, the phosphorylation at Ser289 and Ser293sites is likely to play an important pathological role in AD pathogenesis.Therefore, this work can promote further investigations on the roleof phosphorylation in AD pathogenesis by both the simulation and experimentalmeans.