Table 1.
Statistical analysis of HADDOCK complexes.
The statistical values of the selected PKR complexes were indicated along with their cluster numbers. The Z-score indicates the reliability of selected complexes.
Fig 1.
Structral stability of the PKR complexes.
The time dependent variations of PKR forms in complex with the substrates and inhibitors. (a) shows the RMSD of the backbone atoms (b) RMSF fluctuation of the PKR residues (c) Radius of gyration of PKR forms in the complexes. Residues showing higher RMSF values are marked in the figure.
Fig 2.
Number of intermolecular hydrogen bonds formed by PKR.
The plot showing the number of hydrogen bonds between PKR and the interacting proteins in a time dependent manner.
Table 2.
Salt bridges formed by PKR with the interacting proteins.
Residues of PKR molecules involving in salt bridge formation with the interacting proteins during the course of the simulation. The salt bridges were tabulated along with the numerical values in brackets indicating the distance between N and O atom measured in Å units and percentage of the existence of the salt bridges.
Table 3.
Aromatic interactions and Cation-pi interactions of PKR with the interacting proteins.
Aromatic interactions between the PKR and the interacting proteins formed during the course of simulation within 7 A°. The cation-pi interactions of PKR with the proteins formed during the course of simulation within 6 A°. The minimum distance between the residues is indicated in the brackets.
Fig 3.
Binding energies calulations of PKR with the substrate and the inhibitors.
(a) PKR binding energies with the substrate and the inhibitors. The error bars are indicated by black lines. (b) Residue based decomposition of the binding energies for the activation segment of PKR in the PKR complexes.
Fig 4.
Secondary structural variations of the aloop.
The secondary structral variation of the PKR’s aloop ranging from 438–458 residues. The plots are indicated by (a) PKRpp-eIF2α, (b) PKRpp-K3L, (c) PKRpp-TAT, (d) PKRp-eIF2α, (e) PKRp-K3L and (f) PKRp-TAT. The legend indicates the colors used to represent the secondary structural variations.
Fig 5.
Eigenvector calulations to predict the stability and structral variations of the simulated complexes.
(a) Figure showing the cumulative percentages of the proportional variance contributed by the eigenvectors of the PKR complexes. (b) 2D plot of the projections of the eigenvector 1 and eigenvector 2 showing the essential subspace of the complexes.
Fig 6.
Free energy landscapes of the PKR protein complexes.
The plots are indicated by (a) PKRpp-eIF2α, (b) PKRpp-K3L, (c) PKRpp-TAT, (d) PKRp- eIF2α, (e) PKRp-K3L, (f) PKRp-TAT. Conformations having lower energies retrieved from the Free energy landscapes are marked with a dot in the square. The energy bars indicate binding free energy in KJ/mol.
Fig 7.
Electrostatic potential maps of the binding surfaces of PKR complexes.
The electrostatic potential maps of the binding surfaces along with the activation loop of PKR are shown for the selected stuctres from the free energy landscape plot. Figs 1, 3 and 5 indicate PKRpp bound to eIF2α, K3L and TAT. Figs 2, 4 and 6 indicate PKRp bound to eIF2α, K3L and TAT. The region in red color indicate high electronegative regions and the regions in blue color indicate electropositive regions. The color bars are calibrated in kcal/mol/e.
Fig 8.
Domain movements of PKR in the protein protein complexes.
Effective rotation axes and perpendicular centroid-connecting lines are rendered as tubes in the color of the corresponding domain. The arrows indicate a left-hand rotation, indicating a shift in the center of mass of the domain from the first structure to the second structure. The plots are indicated by (a) PKRpp-eIF2α, (b) PKRpp-K3L, (c) PKRpp-TAT, (d) PKRp-eIF2α, (e) PKRp-K3L, (f) PKRp-TAT. Reference domain, Domain 1 and Domain 2 are indicated by Blue, Red and Black respectively. The arrows drawn indicate the direction of the domain motion.
Fig 9.
Cross-correlation heat maps of the PKR protein.
Cross-correlation heat map generated using the PCA vectors showing the correlated and anti-correlated regions in the protein structure. The plots are indicated by (a) PKRpp-eIF2α, (b) PKRpp-K3L, (c) PKRpp-TAT, (d) PKRp-eIF2α, (e) PKRp-K3L, (f) PKRp-TAT. The P, N lobes and the activation segment are demarked by a boxed structure.