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


Barredo P.A. Fernandez M.J.F. Ambe C.E. Balanay M.P.
October 2021Public Library of Science

PLoS ONE
2021#16Issue 10 October

The microtubule-binding protein tau has been the center of researches concerning Alzheimers 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.



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Department of Chemistry, Iligan Institute of Technology, Mindanao State University, Iligan, Philippines
Department of Chemistry, Nazarbayev University, Nur-Sultan, Kazakhstan

Department of Chemistry
Department of Chemistry

10 лет помогаем публиковать статьи Международный издатель

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