TAU FIBRIL WITH MEMBRANE LIPIDS: INSIGHT FROM COMPUTATIONAL MODELING AND SIMULATIONS
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Date
2021-10-15
Authors
Barredo, Prechiel A.
Fernandez, Marvin Jose F.
Ambe, Christopher E.
Balanay, Mannix P.
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS ONE
Abstract
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.
Description
Keywords
Type of access: Open Access, membrane lipids, Tau fibril
Citation
Barredo, P. A., Fernandez, M. J. F., Ambe, C. E., & Balanay, M. P. (2021). Tau fibril with membrane lipids: Insight from computational modeling and simulations. PLOS ONE, 16(10), e0258692. https://doi.org/10.1371/journal.pone.0258692