We investigated the conformational change in the human prion protein owing to an Ala117→ Val mutation by using molecular dynamics simulations. This mutation is related to Gerstmann-Sträussler-Sheinker disease, one of the familial prion diseases. Five prion protein structures were simulated in the periodic or non-periodic system. The results of molecular dynamics calculations indicated that the globular domains of wild-type structures (109-228 and 90-228) were stable. In contrast, the globular domains of mutant structures (109-228 and 90-228) were sensitive to the N-terminal region possessing the Ala117→ Val mutation, and the β-sheet regions were increased.