Copper and Zinc Copper and Zinc Coordination mode in Coordination mode in - - Amyloid Peptides Amyloid Peptides A XAS and A XAS and ab initio ab initio study study ABR2008, 10-11 Aprile 2008, Roma ABR2008, 10-11 Aprile 2008, Roma V. Minicozzi V. Minicozzi Phys. Dept.- University of Rome Phys. Dept.- University of Rome Tor Vergata Tor Vergata
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Copper and Zinc Coordination mode in -Amyloid Peptides A XAS and ab initio study ABR2008, 10-11 Aprile 2008, Roma V. Minicozzi Phys. Dept.- University.
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Copper and Zinc Copper and Zinc Coordination mode in Coordination mode in --
Amyloid PeptidesAmyloid Peptides
A XAS and A XAS and ab initio ab initio studystudy
ABR2008, 10-11 Aprile 2008, RomaABR2008, 10-11 Aprile 2008, Roma
V. MinicozziV. MinicozziPhys. Dept.- University of RomePhys. Dept.- University of Rome
Tor VergataTor Vergata
Calculations
DESY -BerlinK. JansenN. Christian
Experiments
CNR- TrentoM. Dalla SerraC. Potrich
EMBL-DESY-HamburgW. Meyer-Glauche
Biophysics Group in Rome
“Tor Vergata”
S. MoranteG. C. RossiV. MinicozziF. StellatoS. Alleva
A. Maiorana
Computations have been performed at
Fermi
BEN
Altix
SummaSummaryry
• A peptide
• XAS results
• ab-initio simulations
• Conclusions and outlook
Alzheimer Disease (AD)Alzheimer Disease (AD)
AD brains show two lesions
1- Amyloid Plaques:
Extracellular deposits of A peptide
almost spherical with a 10-100 mm diameter
2- Neurofibrillar Tangles:
Intracellular abnormal elicoidal fibers mainly composed by tau protein
These two lesions can occur independently of each other
comes from classical MD of Cu+2-A1-16 with Cu+2 bound to Nterm, His6, His13, His14
S1 494 atoms and 13691369 electronsS2 703 atoms and 1951 electronsS3 628 atoms and 1776 electrons
S1: Distances from Cu2+
S2: Distances from Cu2+
Conclusions and OutlookConclusions and Outlook
• We can discriminate via ab-initio simulations among the structural models extracted from XAS experiments
• QM/MM simulations of the whole hydrated A peptide based on structural XAS data expecially relevant for Zn+2 structures where pairs of peptides are involved
• New XAS experiments with Aluminium and Zinc
Thanks for your Thanks for your attention!attention!