Figure 1.
2D topological structure plot of GK.
Figure 2.
Time evolutions along with the wRMSD of the backbone atoms of GK in the simulated structures compared with the reference structure.
Progression of the target wRMSD value is in black; actual values for GK corresponding to the trajectories of B1 and C1-C3 are in red, blue, green, and pink, respectively.
Figure 3.
The conformational transition pathway of GK between the super-open state and the closed state.
The center image is the time dependence of the cleft angle between the two domains in the process of GK activation. Around the upper semicircle of the center image, five snapshots are extracted from trajectory B1 at the activated times of 100 ps, 300 ps, 550 ps, 650 ps and 800 ps. Two crystal structures of GK in the super-open and closed states are shown at either end of the catalytic cycle, and four snapshots at the inactivated times of 150 ps, 400 ps, 600 ps and 800 ps that were found previously are also shown in the lower semicircle (9). Three important components of conformational change in GK are labeled in comment frames. Loop I between the α4 and β7 segments is in red; the β6 and β7 strands are in cyan; helix α13 is in yellow.
Figure 4.
Free energy landscape along the conformational transition pathway of GK activation.
Figure 5.
Time dependency of wRMSDs of the large domain (black line) and small domain (red line) in GK during the TMD simulation.
Figure 6.
Changes in the hydrogen bonds between residues Asp205 and Arg447 and residues Glu216 and Lys458 during the TMD simulation.
(A) Snapshots at 1 ps, 300 ps, 700 ps and 1000 ps. (B) Distances from the Oε1 and Oε2 atoms in Glu216 to the Hζ1, Hζ2 and Hζ3 atoms in Lys458. (C) Distances from the Oδ1 and Oδ2 atoms in Asp205 to the Hη1 and Hη2 atoms in Arg447.
Figure 7.
Changes of the hydrophobic pocket and its hydrophobic interaction to Ile159 along the TMD simulation, with snapshots at 900 ps (A), 920 ps (B), 980 ps (C) and 990 ps (D).
Figure 8.
Process of glucose binding to GK.
(A) The residues of GK in contact with glucose during the TMD simulation, represented by different colors. The colored frame means glucose has contact with the residue, while the blank frame means glucose does not have contact with the residue. (B) Binding affinity between glucose and GK calculated by X-Score. (C) wRMSD of the heavy atoms between the crystal pose and docked pose of glucose.
Figure 9.
An atomic mechanism for the whole catalytic circulation of GK.
The width of the arrow indicates the time scale in the conformational pathway, and yellow dots in the arrow represent the intermediate state of the energy well in the activation-inactivation-activation process.