dorsal/arxiv
View SchemaMolecular Dynamics Simulation of Amyloid Beta Dimer Formation
| Authors | B. Urbanc, L. Cruz, F. Ding, D. Sammond, S. Khare, S. V. Buldyrev, H. E. Stanley, N. V. Dokholyan |
|---|---|
| Categories | |
| ArXiv ID | physics/0403040 |
| URL | https://arxiv.org/abs/physics/0403040 |
| DOI | 10.1529/biophysj.104.040980 |
Abstract
Recent experiments with amyloid-beta (Abeta) peptide suggest that formation of toxic oligomers may be an important contribution to the onset of Alzheimer's disease. The toxicity of Abeta oligomers depends on their structure, which is governed by assembly dynamics. Due to limitations of current experimental techniques, a detailed knowledge of oligomer structure at the atomic level is missing. We introduce a molecular dynamics approach to study Abeta dimer formation: (1) we use discrete molecular dynamics simulations of a coarse-grained model to identify a variety of dimer conformations, and (2) we employ all-atom molecular mechanics simulations to estimate the thermodynamic stability of all dimer conformations. Our simulations of a coarse-grained Abeta peptide model predicts ten different planar beta-strand dimer conformations. We then estimate the free energies of all dimer conformations in all-atom molecular mechanics simulations with explicit water. We compare the free energies of Abeta(1-42) and Abeta(1-40) dimers. We find that (a) all dimer conformations have higher free energies compared to their corresponding monomeric states, and (b) the free energy difference between the Abeta(1-42) and the analogous Abeta(1-40) dimer conformation is not significant. Our results suggest that Abeta oligomerization is not accompanied by the formation of stable planar beta-strand Abeta dimers.
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"abstract": "Recent experiments with amyloid-beta (Abeta) peptide suggest that formation\nof toxic oligomers may be an important contribution to the onset of Alzheimer\u0027s\ndisease. The toxicity of Abeta oligomers depends on their structure, which is\ngoverned by assembly dynamics. Due to limitations of current experimental\ntechniques, a detailed knowledge of oligomer structure at the atomic level is\nmissing. We introduce a molecular dynamics approach to study Abeta dimer\nformation: (1) we use discrete molecular dynamics simulations of a\ncoarse-grained model to identify a variety of dimer conformations, and (2) we\nemploy all-atom molecular mechanics simulations to estimate the thermodynamic\nstability of all dimer conformations. Our simulations of a coarse-grained Abeta\npeptide model predicts ten different planar beta-strand dimer conformations. We\nthen estimate the free energies of all dimer conformations in all-atom\nmolecular mechanics simulations with explicit water. We compare the free\nenergies of Abeta(1-42) and Abeta(1-40) dimers. We find that (a) all dimer\nconformations have higher free energies compared to their corresponding\nmonomeric states, and (b) the free energy difference between the Abeta(1-42)\nand the analogous Abeta(1-40) dimer conformation is not significant. Our\nresults suggest that Abeta oligomerization is not accompanied by the formation\nof stable planar beta-strand Abeta dimers.",
"arxiv_id": "physics/0403040",
"authors": [
"B. Urbanc",
"L. Cruz",
"F. Ding",
"D. Sammond",
"S. Khare",
"S. V. Buldyrev",
"H. E. Stanley",
"N. V. Dokholyan"
],
"categories": [
"physics.bio-ph"
],
"doi": "10.1529/biophysj.104.040980",
"title": "Molecular Dynamics Simulation of Amyloid Beta Dimer Formation",
"url": "https://arxiv.org/abs/physics/0403040"
},
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