Figure 1.
Structural models of double-layer Aβ segmental polymorphism proposed by Eisenberg group.
(A) Schematic representation of the U turn structure of Aβ single layer based on ss-NMR. The first beta sheet (green) and the second beta sheet (yellow) are represented by a thick line. The thin (black) line represents the loop region that connects the two sheets. The crystal structure of Aβ16−21 form II (blue) serves as an interface for model 16–21P (Figure B) and model 16–21AP (Figure C) of Aβ16−21. The model 16–21AP displays antiparallel β sheet. In the model 27–32 (Figure D) interactions between double-layer Aβ is through the crystal structure of Aβ27−32. The model 35–42 in Figure 1 E is based on the crystal structures of Aβ35−42 form II as the interface between double-layer Aβ. The fifth model (Figure 1F) is based on the long steric zipper interfaces consisting of Aβ30−35 and Aβ35−42 microcrystal structure. The blue color is used here to indicate the interfacial hydrophobic interactions based on the microcrystal structures.
Table 1.
Summary of Aβ segmental polymorphic oligomeric models and Simulation Conditions.
Figure 2.
Root Mean Square Deviation (RMSD) and Radius gyration (Rg) for the Aβ segmental polymorphism models.
Variation of the Cα atom root mean square deviation (RMSD) with respect the energy minimized structure of the five segmental polymorphic models of Aβ. The <RMSD> of each model was calculated using two independent trajectories (A). Radius of gyration as a function of time for each structures during the 50 ns MD simulations (B). Red, 16–21P; pink, 16–21AP; blue, 27–32; green, 35–42; yellow, 30–42.
Figure 3.
Comparison of all-atom root-mean-square deviation and solvent accessible surface areas of Aβ segmental polymorphism models.
Backbone Cα atom-positional root-mean-square fluctuations, RMSF, along the amino acid sequence for the five models (A). The results are the average of two independent salutation of each system. The variation of average per residue solvent accessible surface area for each models (B). Red, 16–21P; pink, 16–21AP; blue, 27–32; green, 35–42; yellow, 30–42.
Figure 4.
Time evolution of sheet-to-sheet distances.
The inter-sheet distances for the models 16–21, 27–32, 30–42 and 35–42 were calculated by averaging the mass center distance between backbone residues of 16–21, 27–32, 30–42 and 35–42 respectively. The results are the average of two independent simulation of each system. Red, 16–21P; green, 16–21AP; blue, 27–32; pink, 35–42; cyano, 30–42.
Figure 5.
The structure of the starting configuration of of the interactions of Asp23/Lys28 and Lys16/Glu22 for the double layer 16–21P model.
The positions of the residues originally involved in the formation of the salt bridge are represented in sphere visualization to emphasize their location.
Figure 6.
Average intra-chain salt bridge distance (Aspn23/Lysn23) along the 50 ns simulation for Aβ segmental polymorphs.
The results are the average of two independent simulations and it is the average of the two layers of each system. A) 16–21P B) 16–21AP C) 27–32 D) 35–42 and E) 30–40. Red, 1D23-1K28; pink, 2D23-2K28; blue, 3D23-3K28; green, 4D23-4K28; yellow, 5D23-5K28.
Figure 7.
Average inter-chain salt–bridges (Aspn23/Lysn−123) along simulation for 16–21P, 27–32, 30–40 and 35–42.
The results are the average of two independent simulations and it is the average of the two layers of each system. A) 1621P B) 27–32 C) 35–42 and D) 30–30. Red, 1D23-2K28; pink, 2D23-3K28; blue, 3D23-4K28; green, 4D23-5K28.
Figure 8.
Average inter-sheets salt–bridge distance (Lysn16/Glun22) along simulation for 16–21P and 16–21AP.
A) 16–21P and (B) 16–21AP. The results are the average of two independent simulation of each system. Red, 1K16-1E22; pink, 2K16-2E22; blue, 3K16-3E22; green, 4K16-4E22; yellow, 5K16-5E22. Red, 16–21P; green, 16–21AP; blue, 27–32; pink, 35–42; cyano, 30–42.
Table 2.
Summary of the MM/PBSA Energy (kcal/mol) Component Analysis of the Bilayer Systems of the MD Simulation of the Double Layer Models of Aβ segmental polymorphism.
Figure 9.
Percentage of hydrogen bonds as a function time with respect to the energy minimized structure of Aβ segmental polymorphic models.
Red, 16–21P; green, 16–21AP; blue, 27–32; pink, 35–42; cyano, 30–42.
Figure 10.
Secondary structure variation plot for each of the Aβ segmental polymorphism models.
(A) Aβ16−21P, (B) Aβ16−21AP (C) Aβ27−32, (D) Aβ35−42 and (E) Aβ130−42 interfaces. The secondary structure color codes: red-β-sheet, green-bend, yellow-turn, blue -α-helix, coil-white. Where L stands for the peptide layers number and C stands for the peptide chain number.
Figure 11.
Snapshots from MD simulations for double-layered Aβ segmental polymorphism models with the steric zipper interfaces.
(A) Aβ16−21P, (B) Aβ16−21AP (C) Aβ27−32, (D) Aβ35−42 and (E) Aβ130−42 interfaces at 0ns, 25ns and 50 ns.