Fig 1.
Amino acid sequence of the PHF-Tau protein with the observed b-strand regions and the corresponding schematic view of the C-shaped architecture of the protofilament core with possible high-affinity binding sites of the protofibril (S1 to S5) [35,36].
Fig 2.
Molecular structures and its 3D geometric representations of (a) 3-alpha-cholesterol, (b) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, and (c) C18:1 sphingomyelin.
Fig 3.
(a) The docking conformation of 3-alpha-cholesterol on PHF-Tau showing the H-bond formation between the PHF-Tau backbone and OH group of the ligand. (b) Electrostatic surface potential model on the docking site of 3-alpha-cholesterol on PHF-Tau which shows the hydrophobicity of the binding site (blue regions are hydrophilic and red orange regions are hydrophobic). (c) H-bonds obtained in NBO analysis.
Fig 4.
(a) The docking conformation of 1-POPC on PHF-Tau showing the H-bond formation between 1-POPC and the PHF-Tau backbone. (b) Electrostatic surface potential model on the docking site of 1-POPC ON PHF-Tau which shows the hydrophobicity of the binding site (blue regions are hydrophilic and red orange regions are hydrophobic).
Fig 5.
Intermolecular interactions between 1-POPC and PHF-Tau based on NBO analysis.
Interatomic distance is shown in angstrom.
Fig 6.
(a) The docking conformation of C18:1 Sphingomyelin on PHF-Tau showing the H-bond formation between C18:1 Sphingomyelin and the PHF-Tau backbone. (b) Hydrophobicity of the binding site (blue regions are hydrophilic and red orange regions are hydrophobic).
Fig 7.
NBO analysis of the intermolecular interactions between PHF-Tau and C18:1 Sphingomyelin.
(a) H-bond formation between C18:1 Sphingomyelin and the PHF-Tau backbone and (b) significant London dispersion forces. Interatomic distances are shown in angstrom.
Fig 8.
Variations of RMSD values in molecular dynamics simulations of the three membrane lipids.
Fig 9.
Kinetic, potential and temperature variations in molecular dynamics simulations of of 3-alpha-cholesterol docked structure with RMSD = 0.
Fig 10.
Kinetic, potential and temperature variations in molecular dynamics simulations of 1-POPC docked structure with RMSD = 0.
Fig 11.
Kinetic, potential and temperature variations in molecular dynamics simulations of C18:1Sphingomelin docked structure with RMSD = 0.
Fig 12.
Variations of RMSD values in molecular dynamics simulation of PHF-Tau protofilament and PHF-Tau protofilament with 1-POPC.
Fig 13.
Ligand (AM1-BCC optimized structure) embedded in PHF-Tau protofilament (tail side); RMSD = 0.
Hydrophobicity surface is shown. Solvent used is water. Inset shows the preferred configuration of the the ligand: (a) cholesterol; (b) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; and (c) C18:1 sphingomyelin and their interactions with the protein.
Fig 14.
The docked structures of lipids with RMSD = 0 in solvated and unsolvated PHF-Tau.
(a) cholesterol; (b) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; and (c) C18:1 sphingomyelin.
Fig 15.
Variations of RMSD values in molecular dynamics simulations of the three membrane lipids in solvated protein.