title: Insights into structural properties of denatured human prion 121-230 at melting temperature studied by replica exchange molecular dynamics.
abstract: Misfolding and aggregation of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. PrP undergoes structural conversion from a natively folded state into a misfolded state, resulting in aggregated amyloid fibrils. Partial unfolding has been recognized as an essential step in fibrillation, especially at the middle point of unfolding. To study the possible aggregation-prone states, we characterized the structure of the C-terminal globular domain of human prion (huPrP) 121-230 near extended conformation at melting temperature by replica exchange molecular dynamics (REMD) simulation, as the REMD method is the most suited generalized-ensemble algorithm that performs random walk in energy space and promotes a system to escape from local energy traps. Our results revealed that denatured huPrP is partially folded with α-helical structure at melting temperature. The simulation results provide further insight into the unfolding of prion, which is essential in pathogenesis of prion diseases.
authors.affiliation: Department of Physics, National Chung Cheng University, Ming-Hsiung Chia-Yi, Taiwan 62102, ROC.
authors.forename: Jaw-Luen
authors.initials: JL
authors.lastname: Tang
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Wu
authors.forename: Shing-Chuen
authors.initials: SC
authors.lastname: Wang
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Lee
mesh_terms: D002942:Circular Dichroism; D016000:Cluster Analysis; D006801:Humans; D056004:Molecular Dynamics Simulation; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D011328:Prions; D011994:Recombinant Proteins