Theconformational polymorphism of this loop in PrPC playsa long debating role in the susceptibility and development of TSE.42 Using state-of-the-art MD methods in combinationwith NMR data, we designed the conformational landscapes of the β2−α2loop to describe the Nb484-HuPrP recognition mechanisms in the WTand predict the behavior of this epitope in the E219K and V210I. Here, PRNP is linked to human prion disease.