Open AccessTau fibril with membrane lipids: Insight from computational modeling and simulations
Author(s) -
Prechiel A. Barredo,
Marvin Jose F. Fernandez,
Christopher E. Ambe,
Mannix P. Balanay
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0258692
Subject(s) - molecular dynamics , docking (animal) , chemistry , biophysics , protein data bank (rcsb pdb) , molecular model , molecular mechanics , phosphocholine , sphingomyelin , lipid bilayer , tau protein , affinities , crystallography , stereochemistry , biochemistry , computational chemistry , membrane , biology , alzheimer's disease , phosphatidylcholine , phospholipid , medicine , nursing , disease , pathology
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.