title: Copper binding sites in the C-terminal domain of mouse prion protein: A hybrid (QM/MM) molecular dynamics study.
abstract: We present a hybrid QM/MM Car-Parrinello molecular dynamics study of the copper-loaded C-terminal domain of the mouse prion protein. By means of a statistical analysis of copper coordination in known protein structures, we localized the protein regions with the highest propensity for copper ion binding. The identified candidate structures were subsequently refined via QM/MM simulations. Their EPR characteristics were computed to make contact with the experimental data and to probe the sensitivity to structural and chemical changes. Overall best agreement with the experimental EPR data (Van Doorslaer et al., J Phys Chem B 2001; 105: 1631-1639) and the information currently available in the literature is observed for a binding site involving H187. Moreover, a reinterpretation of the experimental proton hyperfine couplings was possible in the light of the present computational findings.
authors: Laboratory of Computational Chemistry and Biochemistry, Institute of Chemical Sciences and Engineering, EPFL, CH-1015 Lausanne, Switzerland.
authors: Maria Carola
authors: MC
authors: Colombo
authors: Joost
authors: J
authors: Vandevondele
authors: Sabine
authors: S
authors: Van Doorslaer
authors: Alessandro
authors: A
authors: Laio
authors: Leonardo
authors: L
authors: Guidoni
authors: Ursula
authors: U
authors: Rothlisberger
mesh_terms: D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D000072002:Prion Proteins; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D003300:Copper