title: Molecular dynamics as an approach to study prion protein misfolding and the effect of pathogenic mutations.
abstract: Computer simulation of protein dynamics offers unique high-resolution information that complements experiment. Using experimentally derived structures of the natively folded prion protein (PrP), physically realistic dynamics and conformational changes can be simulated, including the initial steps of misfolding. By introducing mutations in silico, the effect of pathogenic mutations on PrP conformation and dynamics can be assessed. Here, we briefly introduce molecular dynamics methods and review the application of molecular dynamics simulations to obtain insight into various aspects of the PrP, including the mechanism of misfolding, the response to changes in the environment, and the influence of disease-related mutations.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195-5013, USA.
authors.forename: Marc W
authors.initials: MW
authors.lastname: van der Kamp
authors.forename: Valerie
authors.initials: V
authors.lastname: Daggett
mesh_terms: D000818:Animals; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation; D017096:Prion Diseases / Q000235:genetics* / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000235:genetics*; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D012984:Software
chemical_list: D011328:Prions; D011994:Recombinant Proteins