Tau fibril with membrane lipids: Insight from computational modeling and simulations

The microtubule-binding protein tau has been the center of researches concerning Alzheimer's disease (AD) due to several clinical trials of β-amyloid therapies failing recently. The availability of the tau fibril structure from AD brain enables computational modeling studies to calculate bindin...

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Bibliographic Details
Published in:PloS one 2021-10, Vol.16 (10), p.e0258692-e0258692
Main Authors: Barredo, Prechiel A, Fernandez, Marvin Jose F, Ambe, Christopher E, Balanay, Mannix P
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amino acids
Analysis
Binding sites
Biology and Life Sciences
Cholesterol
Cholesterol - metabolism
Clinical trials
Computational neuroscience
Dementia
Energy value
FDA approval
Filaments
Health aspects
Humans
Ligands
Lipids
Medicine and Health Sciences
Membrane lipids
Membrane Lipids - metabolism
Models, Molecular
Molecular docking
Molecular Docking Simulation
Molecular dynamics
Molecular Dynamics Simulation
Neurodegenerative diseases
Pathology
Phosphatidylcholines - metabolism
Phosphocholine
Phosphorylation
Physical Sciences
Potential energy
Protein Structure, Secondary
Proteins
Simulation
Solvation
Sphingomyelin
Sphingomyelins - metabolism
Tau protein
Tau proteins
tau Proteins - chemistry
tau Proteins - metabolism
β-Amyloid
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Summary:The microtubule-binding protein tau has been the center of researches concerning Alzheimer's disease (AD) due to several clinical trials of β-amyloid therapies failing recently. The availability of the tau fibril structure from AD brain enables computational modeling studies to calculate binding affinities with different ligands. In this study, the tau paired helical filaments (PHF-Tau) (PDB ID: 5O3L) was used as receptor and interactions with the lipids: 3-alpha-cholesterol; 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; and C18:1 sphingomyelin, were explored with molecular docking, molecular dynamics, and natural bond orbital analysis. Docking sites upon solvation of the protein with transferable interatomic potential-3 points reveal the amphipathic nature of PHF-Tau and molecular dynamics simulations show that the embedded phosphocholine at the tail side gives high potential energy values with some amino acids forming H-bond interactions.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0258692