Molecular dynamics simulation on the effect of transition metal binding to the N-terminal fragment of amyloid-β

Figures & data

Figure 1. Metal binding modes used in this study. Top row, left-right: Fe_1, Fe_2 and Fe_3. Bottom row, left-right: Cu and Zn.

Figure 2. Backbone RMSD values (Å) for the simulations of Fe_1, Fe_2 and Fe_3.

Table 1. Total percentage of secondary structure, by type, for Fe(II)–Aβ complexes.

Secondary structure	Helix	Sheet	Other
Fe_1	15.49	0.23	84.28
Fe_2	17.20	0.09	82.71
Fe_3	18.52	0.04	81.44

Figure 3. RMSF data (Å) for three different Fe coordination modes.

Table 2. Percentage of secondary structure types observed over equilibrated trajectories.

SS %	Helix	Sheet	Other
Cu	16.28	0.00	83.72
Fe_1	15.49	0.23	84.28
Zn	22.19	0.00	77.81

Table 3. Statistics of hydrogen bond occupation.

# Hydrogen bonds	Ave	SD	Min	Max
Cu	5.32	2.17	0	15
Fe_1	7.33	1.90	0	15
Zn	4.55	1.65	0	9

Figure 4. Secondary structure plots, Ramachandran and residue contact maps for Fe(II)–Aβ complexes.

Figure 5. Minimised geometry and clustering percentage of three Fe(II) complexes.

Figure 6. Backbone RMSD values (Å) for the simulations of Cu, Fe_1 and Zn.

Table 4. Summary of bond critical point propertiesa for metal–ligand bonds (au).

Metal	Ligand	ρ	∇^2ρ	ε	G	V	H
Cu	N (Asp1)	0.085	0.249	0.013	0.097	−0.131	−0.035
	O (Asp1)	0.085	0.363	0.030	0.118	−0.146	−0.028
	N (His6)	0.098	0.339	0.047	0.126	−0.168	−0.042
	N (His14)	0.094	0.316	0.063	0.118	−0.158	−0.040
Fe	N (Asp1)	0.079	0.419	0.371	0.113	−0.122	−0.009
	O (Asp1)	0.075	0.432	0.893	0.112	−0.115	−0.004
	O (His6)	0.066	0.421	1.165	0.105	−0.106	0.000
	N (His6)	0.085	0.501	0.702	0.134	−0.143	−0.009
	N (His14)	0.079	0.482	0.483	0.125	−0.130	−0.005
Zn	O (Asp1)	0.074	0.293	0.047	0.096	−0.119	−0.023
	N (His 6)	0.075	0.236	0.068	0.087	−0.114	−0.028
	O (Glu11)	0.053	0.205	0.063	0.061	−0.070	−0.010
	N (His14)	0.082	0.256	0.057	0.098	−0.131	−0.034

^aρ is the electron density at the bond critical point; ▿2ρ is the Laplacian of the electron density here; ε is the ellipticity of the bond; G is the kinetic energy density at the bond critical point; V is the potential energy density here; H is the total energy density, the sum of G + V.

All properties are reported in atomic units.

Figure 7. RMSF values (Å) for Cu, Fe_1 and Zn structures.

Figure 8. Breakdown of secondary structure and Ramachandran maps for Cu, Fe_1 and Zn complexes with Aβ1–16.

Figure 9. Occupancy of salt bridges and contact maps for Cu, Fe_1 and Zn complexes.

Figure 10. Plots of hydrogen bond occupancy for Cu (left), Fe_1 (centre) and Zn (right). Plots only display data for hydrogen bonds present for greater than 5% of simulation. Black circles indicate multiple interactions between relevant residues.

Figure 11. Summary of clustering analysis: minimised geometry, percentage occupancy and molecular mechanics energy (kcal/mol) after minimisation.