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.

Minicozzi, V., Morante, S., Rossi, G., 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 (pp.1992-2015). HOBOKEN : JOHN WILEY & SONS INC [10.1002/qua.21724].

The role of metals in amyloid aggregation - Experiments and ab initio simulations

MINICOZZI, VELIA;MORANTE, SILVIA;Stellato, F.;
2008-01-01

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.
3rd International Theoretical Biophysics Symposium
Cetraro, ITALY
JUN 16-20, 2007
Rilevanza internazionale
su invito
2008
Settore FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA)
English
Absorption; Agglomeration; Amines; Atomic spectroscopy; Binding energy; Binding sites; Copper; Glycoproteins; Metals; Structural metals; X ray spectroscopy; Ab Initio simulations; Alzheimer disease (AD); Amyloid Peptides; Atomic structures; First principles; Metal-binding sites; Physico chemicals; Spectroscopic techniques; X-ray absorption (XANES) spectroscopies; Absorption spectroscopy
Intervento a convegno
Minicozzi, V., Morante, S., Rossi, G., 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 (pp.1992-2015). HOBOKEN : JOHN WILEY & SONS INC [10.1002/qua.21724].
Minicozzi, V; Morante, S; Rossi, G; Stellato, F; Christian, N; Jansen, K
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/37309
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