The result showed that the number of hub nodes increased markedly when the degree of the residue hub was low. Finally, the cluster network analysis was displayed as a detailed map of the residue interaction network that could detect densely interconnected modules in local networks. Figure 5.
The cluster network analysis. A General overview and B a detailed close-up of the network of cluster in the wild-type structure. It worth to noting that through the network analysis of the representative structures from the latter two equilibrium trajectories Figures S10 , S11 , we found that for the wild-type Cb DPEase and Y68 and G mutant, the differences in the number of cliques and communities, the trend of the hubs, and the intensities of the clusters were highly compatible with the above conclusions.
Overall, site-directed mutagenesis of Y68 and G of the Cb DPEase may induce more stable interactions than that of the wild-type Cb DPEase in the local network, which corresponded to the high level of cooperativity that may affect the catalytic activity of Cb DPEase.
Active site: hydrogen bonds The heme in LiP is not covalently linked to the protein, but held in place by a network of hydrogen bonds. Bader, U. In particular, the two monomeric LiP units are not covalently linked, but they are in contact through one loop from residue to and from to that resulted to be quite flexible during the simulation. Platen Ed. Skeel Eds.
Reliable free energy calculations based on the first two equilibrium trajectories were performed to assess the quantitative effects of the binding affinities between the protein and the ligand. This showed that the vdW energy, polar solvation energy, and nonpolar solvation energy did not significantly contribute to the disparity of binding free energy.
Table 2. And the contributions of non-polar part, polar part, and conformational entropy to the binding free energies were in line with previous results. The surrounding amino acids displayed around the contour demonstrated the frequency they participated in the tunnel boundary in the light of the hydrophobicity and the partial charge of atoms. Figure 6. Figure 7.
Furthermore, the hydrogen bond interactions between the protein and the ligand were detected. It assisted in the understanding of the dissociation pathways and provides some vital clues for improving the catalytic efficiency by the site-directed mutagenesis of Y68 and G Hereafter, certain hydrophobic residues e. During the dissociation, the number of hydrogen bonds that changed between D-fructose and tunnel residues along the reaction coordinate were shown in Figure 8.
Thereafter, the number of hydrogen bonds continued to be more than that of the wild-type Cb DPEase. Table 3. Figure 8.
Figure 9. The detailed location of A—H , along the dissociation process at 4, 7. The residues forming hydrogen bonds red dashed line in ligand dissociation are highlighted in green. The residues participating in the other interactions are highlighted in blue. The D-fructose is highlighted in yellow. Subnetwork analyses of the D-fructose are displayed as two-dimensional view. Figure The residues participating in the other interactions are highlighted in cyan.
The detailed analysis along the reaction coordinate for the unbinding pathway of the wild-type Cb DPEase was displayed in Figure 9. Then at 7. Nevertheless, the residues that formed hydrogen bonds with the substrate were constantly varying. Moreover, D-fructose was also fastened by functional residues in active sites Y6, E34, I35, G67, G69, G, G, E, and E and mutated residues I68 and P through the interatomic contact and combined interactions.
Thus, the free energy located at a platform level Figure 10D. After this plateau period of free energy, a rapid increase occured because of the strong hydrogen bond interactions between the substrate and the tunnel residues.
It was apparent that the benzene ring of the F in the wild-type Cb DPEase flipped in a great fluctuant way. From the structure diagram Figure 11A , we could clearly see that F and W located at the entrance tunnel, which could act as the gatekeeper to regulate the opening of tunnel. Lastly, the free energy was increased continually until the D-fructose was fully dissociated after 28 ns. JZ wrote and revised this paper. YL and JW prepared the tables. ZY made the Supplementary Materials. YL provided some revision advice.
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