Effect of Ionic Strength on Conformational Behavior of Beta Amyloids. A Computational Study.
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| Year of publication | 2009 |
| Type | Conference abstract |
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| Description | Extracellular proteic plaques found in the brains of patients affected by Alzheimers disease contain fibrils composed of beta-amyloid (Abeta) peptides. These range in length from 39 to 43 amino acids, the most abundant form being Abeta-(1-42). The Abeta-(1-42) peptide nucleates and aggregates more rapidly than shorter Abeta peptides [1-3]. It indicates that the C-terminus sequence is critical for the nucleation of amyloid formation and suggesting that production of Abeta-(1-42) may be pathogenic. Although human and rat Abeta-(1-42) peptides differ only by 3 amino acids (positions 5, 10 and 13), they show different cerebral deposition during aging [4]. It indicates the differences in conformational behavior of both peptides. We have performed long range molecular dynamics simulations of both peptides in explicit solvent with different ionic strength. The stability of the secondary structures of the peptides and formation of intramolecular hydrogen bonds were investigated. The AMBER molecular modeling package was used for MD simulations and analyses of results. The NMR solved structure of human Abeta-(1-42) peptide from the PDB database (pdb code 1z0q) was used as starting point of the simulations. The rat Abeta-(1-42) peptide have been prepared using the Triton and Modeller software from human Abeta-(1-42) peptide by in silico mutation method. Each molecule was immersed into octahedral simulating box with TIP3P water molecules (minimal thickness of water layer was 12 A) and counter ions were added to neutralize electrostatic charge of the molecule. |
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