The role of metals in amyloid aggregation - Experiments and ab initio simulations (Articolo in rivista)

Type
Label
  • The role of metals in amyloid aggregation - Experiments and ab initio simulations (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Alternative label
  • Minicozzi, V; Morante, S; Rossi, GC; Stellato, F; Christian, N; Jansen, K (2008)
    The role of metals in amyloid aggregation - Experiments and ab initio simulations
    in International journal of quantum chemistry
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Minicozzi, V; Morante, S; Rossi, GC; Stellato, F; Christian, N; Jansen, K (literal)
Pagina inizio
  • 1992 (literal)
Pagina fine
  • 2015 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 108 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • \"[Minicozzi, V.; Morante, S.; Rossi, G. C.; Stellato, F.] Univ Roma Tor Vergata, INFN, Dipartimento Fis, Sezione Rome Tor Vergata, I-00133 Rome, Italy; [Morante, S.] Univ Roma La Sapienza, CRS SOFT, Dipartimento Fis, I-00185 Rome, Italy; [Christian, N.] Humboldt Univ, Dept Biol, D-10115 Berlin, Germany; [Jansen, K.] DESY, NIC, D-15738 Zeuthen, Germany (literal)
Titolo
  • The role of metals in amyloid aggregation - Experiments and ab initio simulations (literal)
Abstract
  • With a combination of modern spectroscopic techniques and numerical first principle simulations it is possible to investigate the physico-chemical basis of the P-amyloid aggregation phenomenon, which is suspected to be at the basis of the development of the Alzheimer disease. On the experimental side, in fact, X-ray absorption spectroscopy can be successfully used to determine the atomic structure around the metal binding site in samples where P-amyloid peptides are complexed with either Cu2+ or Zn2+ ions. Exploiting spectroscopic information obtained on a selected set of fragments of the natural A beta-peptide, the residues that along the sequence are coordinated to the metal are identified. Although copper data can be consistently interpreted assuming that oligopeptides encompassing the minimal 1-16 amino acidic sequence display a metal coordination mode which involves three Histidines (HiS(6), HiS(13), and His(14)), in complexes with zinc a four Histidines coordination mode is seen to be preferred. Lacking a fourth Histidine in the A beta(1-16) fragment, this geometrical arrangement hints to a Zn2+ promoted inter-peptide aggregation mode. On the theoretical side, first principle ab initio molecular dynamics simulations of the Car-Parrinello type, which have proved to be of invaluable help in understanding the microscopic mechanisms of chemical bonding both in solid-state physics and structural biophysics, have been employed in an effort to give a microscopic basis and find a phenomenological interpretation of the body of available experimental data on A beta-peptides-metal complexes. Using medium size PC-clusters as well as larger parallel platforms, it is possible to deal with systems comprising 300-500 atoms and 1,000-2,000 electrons for simulation times as long as 2-3 ps. We present structural results that nicely compare with NMR and XAS data. (c) 2008 Wiley Periodicals, Inc. (literal)
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