Characterizing the denatured state of human prion 121-230

Misfolding and aggregation of the prion protein (PrP) are responsible for the development of fatal transmissible neurodegenerative diseases. PrP undergoes structural conversion from a natively folded state into a misfolded state, resulting in insoluble amyloid fibrils. Partial unfolding has been recognized as an essential step in fibrillation. The strong correlation of unfolding and fibrillation emphasizes the importance of denatured states. To gain insight into possible aggregation-prone denatured states, we characterized the denatured state of human prion (huPrP) 121-230 near extended conformation by self-guided Langevin dynamics simulations. Our results revealed that denatured huPrP is partially folded with α-helical structure.