Folding simulation of amyloid β-peptide in alzheimer's disease.
An amyloid β-peptide (Aβ) containing 42 residues is a major component of neurotic plaques in Alzheimer’s disease. The conformation of residues 1-28 of the peptide sequence determine whether the amyloid β-peptide will form neurotic aggregates, since the rest of the residues remain in β-sheet conforma...
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| Format: | Final Year Project |
| Language: | English |
| Published: |
2010
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| Online Access: | http://hdl.handle.net/10356/39874 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | An amyloid β-peptide (Aβ) containing 42 residues is a major component of neurotic plaques in Alzheimer’s disease. The conformation of residues 1-28 of the peptide sequence determine whether the amyloid β-peptide will form neurotic aggregates, since the rest of the residues remain in β-sheet conformation. In this project, two runs of molecular dynamics (MD) simulations were performed to model the folding of Aβ(1-28) at dielectric constants 80 and 46.7, representing solvents H2O/D2O(9:1) and H2O/trifluoroethanol-d3(4:6) respectively. Using AMBER6 software, molecular dynamic simulations were performed starting from the linear structure. The structure obtained at dielectric constant of 80 was closer to the nuclear magnetic resonance (NMR) structure, forming a helix with a kink centered near V12. Unfortunately, the angle of bending differed from the NMR structure, such that residues D1-Y10 were very far off from the NMR structure. However, the structure obtained at dielectric constant of 46.7 did not form an α-helix. The results of the MD simulations were then analyzed using root mean square deviation (RMSD), definition of secondary structure of proteins (DSSP), helix content and free energy landscape. |
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