Molecular dynamics simulations of Alzheimer's BACE1 and BACE2 transmembrane domains in neurons: Impact of cholesterol
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...
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Published in | Revista Facultad de Ingeniería no. 98; pp. NP - 128 |
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Main Authors | , , , |
Format | Journal Article |
Language | English Portuguese |
Published |
Medellín
Universidad de Antioquía
01.03.2021
Facultad de Ingeniería, Universidad de Antioquia Universidad de Antioquia |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 0120-6230 2422-2844 2422-2844 |
DOI: | 10.17533/udea.redin.20200368 |