Molecular dynamics simulations of Alzheimer's BACE1 and BACE2 transmembrane domains in neurons: Impact of cholesterol




modal analysis, complex modes, 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.

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Author Biographies

Juan Carlos Cruz-Jiménez, University of Los Andes

Assistant Professor, Department of Biomedical Engineering.

Marcela Mercado-Montoya, University of Antioquia

Research Group in Bioinstrumentation and Clinical Engineering, Bioengineering Program, Faculty of Engineering.

Carlos Eduardo Ostos-Ortíz, University of Antioquia

Faculty of Exact and Natural Sciences, Institute of Chemistry. Teacher.

Alher Mauricio Hernández-Validivieso, University of Antioquia

Professor, Department of Bioengineering. Research Group in Bioinstrumentation and Clinical Engineering, Bioengineering Program, Faculty of Engineering.


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How to Cite

Cruz-Jiménez, J. C., Mercado-Montoya, M., Ostos-Ortíz, C. E., & Hernández-Validivieso, A. M. (2021). Molecular dynamics simulations of Alzheimer’s BACE1 and BACE2 transmembrane domains in neurons: Impact of cholesterol. Revista Facultad De Ingeniería Universidad De Antioquia, (98), 117–128.

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