title: Molecular dynamics study of the beta amyloid peptide of Alzheimer's disease and its divalent copper complexes.
abstract: The Abeta1-42 monomer structure was assessed with a 790 ns molecular dynamics (MD) simulation, and the results were compared with the NMR experiment on Abeta10-35 and Abeta1-40. Previous theoretical work in a model of the His13-His14 region of Abeta defined the possible Cu(II) binding geometries at this site (Raffa et al. J. Biol. Inorg. Chem. 2005, 10, 887-902). MD simulations totalling almost 2 micros were also carried out on Cu(II)/Abeta1-42 systems, using the ab initio structures as templates for the copper binding site. This work finds that the copper-free Abeta1-42 system may stabilize after approximately 350 ns into a collapsed coil conformation, and we find good agreement with some, but not all, of the structural features determined experimentally for the Abeta10-35 and Abeta1-40 peptides. The results of the Cu(II)/Abeta1-42 systems are compared to the Cu(II)-free Abeta1-42 simulation.
authors: Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
authors: Duilio F
authors: DF
authors: Raffa
authors: Arvi
authors: A
authors: Rauk
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D003300:Copper / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D009942:Organometallic Compounds; D014867:Water; D003300:Copper