Molecular dynamics simulations of Alzheimer's BACE1 and BACE2 transmembrane domains in neurons: Impact of cholesterol
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| Format: | Artículo científico |
| Sprache: | en |
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Universidad de Antioquia
2021
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| author | Juan Carlos Cruz-Jiménez |
| author_facet | Juan Carlos Cruz-Jiménez |
| contents | Molecular dynamics simulations of Alzheimer's BACE1 and BACE2 transmembrane domains in neurons: Impact of cholesterol Juan Carlos Cruz-Jiménez Marcela Mercado-Montoya Carlos Eduardo Ostos-Ortíz Alher Mauricio Hernández-Valdivieso Ingeniería complex modes Modal analysis structural analysis molecular interaction Molecular dynamic (MD) simulation is an approach frequently employed in computational biology for exhaustive sampling of the protein-ligand conformational space. Hence, it is useful for structural analysis and the study of molecular interactions. In this study, we report on a MD simulation protocol to understand the dynamics of β-secretase 1 (BACE1) and 2 (BACE2), widely known to play a critical role in the etiology of Alzheimer’s disease, by a structure change evaluation of their transmembrane domains while inserted in a simulated neural membrane system. We considered two different levels in membrane cholesterol content. Because there is no evidence supporting the capacity of BACE1 and BACE2 to exist as a dimer, single and double (BACE1/BACE1, BACE2/BACE2, BACE1/BACE2) systems, either in parallel or antiparallel orientation, were prepared for each run. Analysis of tridimensional structure of BACE1 and BACE2, after 10ns of MD simulation, revealed a correlation between higher cholesterol levels and both peptide refolding and changes in the secondary structure of both transmembrane domains in single and double systems. Interestingly, our results also indicate a potential interaction in the double system BACE2/BACE2, particularly when the domains had an antiparallel orientation. 2021 artículo científico 0120-6230 https://www.redalyc.org/articulo.oa?id=43067842011 https://www.redalyc.org/journal/430/43067842011/ https://www.redalyc.org/journal/430/43067842011/html/ https://www.redalyc.org/journal/430/43067842011/43067842011.epub https://www.redalyc.org/journal/430/43067842011/movil 10.17533/udea.redin.20200368 en http://www.redalyc.org/revista.oa?id=430 Revista Facultad de Ingeniería Universidad de Antioquia application/pdf Universidad de Antioquia Revista Facultad de Ingeniería Universidad de Antioquia (Colombia) Num.98 |
| format | Artículo científico |
| id | redalyc_43067842011 |
| institution | Redalyc |
| language | en |
| publishDate | 2021 |
| publisher | Universidad de Antioquia |
| spellingShingle | Molecular dynamics simulations of Alzheimer's BACE1 and BACE2 transmembrane domains in neurons: Impact of cholesterol Juan Carlos Cruz-Jiménez Ingeniería complex modes Modal analysis structural analysis molecular interaction Molecular dynamics simulations of Alzheimer's BACE1 and BACE2 transmembrane domains in neurons: Impact of cholesterol Juan Carlos Cruz-Jiménez Marcela Mercado-Montoya Carlos Eduardo Ostos-Ortíz Alher Mauricio Hernández-Valdivieso Ingeniería complex modes Modal analysis structural analysis molecular interaction Molecular dynamic (MD) simulation is an approach frequently employed in computational biology for exhaustive sampling of the protein-ligand conformational space. Hence, it is useful for structural analysis and the study of molecular interactions. In this study, we report on a MD simulation protocol to understand the dynamics of β-secretase 1 (BACE1) and 2 (BACE2), widely known to play a critical role in the etiology of Alzheimer’s disease, by a structure change evaluation of their transmembrane domains while inserted in a simulated neural membrane system. We considered two different levels in membrane cholesterol content. Because there is no evidence supporting the capacity of BACE1 and BACE2 to exist as a dimer, single and double (BACE1/BACE1, BACE2/BACE2, BACE1/BACE2) systems, either in parallel or antiparallel orientation, were prepared for each run. Analysis of tridimensional structure of BACE1 and BACE2, after 10ns of MD simulation, revealed a correlation between higher cholesterol levels and both peptide refolding and changes in the secondary structure of both transmembrane domains in single and double systems. Interestingly, our results also indicate a potential interaction in the double system BACE2/BACE2, particularly when the domains had an antiparallel orientation. 2021 artículo científico 0120-6230 https://www.redalyc.org/articulo.oa?id=43067842011 https://www.redalyc.org/journal/430/43067842011/ https://www.redalyc.org/journal/430/43067842011/html/ https://www.redalyc.org/journal/430/43067842011/43067842011.epub https://www.redalyc.org/journal/430/43067842011/movil 10.17533/udea.redin.20200368 en http://www.redalyc.org/revista.oa?id=430 Revista Facultad de Ingeniería Universidad de Antioquia application/pdf Universidad de Antioquia Revista Facultad de Ingeniería Universidad de Antioquia (Colombia) Num.98 |
| title | Molecular dynamics simulations of Alzheimer's BACE1 and BACE2 transmembrane domains in neurons: Impact of cholesterol |
| topic | Ingeniería complex modes Modal analysis structural analysis molecular interaction |
| url | https://www.redalyc.org/articulo.oa?id=43067842011 https://www.redalyc.org/journal/430/43067842011/ https://www.redalyc.org/journal/430/43067842011/html/ https://www.redalyc.org/journal/430/43067842011/43067842011.epub https://www.redalyc.org/journal/430/43067842011/movil |