In the present study we have used molecular dynamics simulations to study the stability of the antiparallel beta-sheet in cellular mouse prion protein (PrPC) and in the D178N mutant. In particular, using the recently developed non-Markovian metadynamics method, we have evaluated the free energy as a function of a reaction coordinate related to the beta-sheet disruption/growth. We found that the antiparallel beta-sheet is significantly weaker in the pathogenic D178N mutant than in the wild-type PrPC. The destabilization of PrPC beta-structure in the D178N mutant is correlated to the weakening of the hydrogen bonding network involving the mutated residue, Arg164 and Tyr128 side chains. This in turn indicates that such a network apparently provides a safety mechanism for the unzipping of the antiparallel beta-sheet in the PrPC. We conclude that the antiparallel beta-sheet is likely to undergo disruption rather than growth under pathogenic conditions, in agreement with recent models of the misfolded monomer that assume a parallel beta-helix.