Molecular docking study of various Enterovirus—A71 3C protease proteins and their potential inhibitors

Figures

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  FIGURE 1. Clustering of models generated from the exhaustiveness optimization between ligand Rupintrivir and 3Cpro protein of 5C1U (PDB ID) with value (A) 8 (default), (B) 16, (C) 32, (D) 64, (E) 128, (F) 256, and (G) 512. The figure was illustrated by Python-based Molecular View with ribbon-shaped proteins and atom-shaped ligands.

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  FIGURE 2. The correlation between exhaustiveness values and docking scores of each 20 binding poses of the system 5C1U—Rupintrivir. The correlation was calculated and drawn by RStudio followed logarithmic trendline with R correlation coefficiency 0.881 (p-value < 0.001).

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  FIGURE 3. The consistency between in silico with in vitro experiments: (A) six popular clusters with different colors were made between 21 candidates with the 5C1U: red—cluster 1, green—cluster 2, purple—cluster 3, yellow—cluster 4, blue—cluster 5, and pink—cluster 6; and the crystallography model of (B) 3SJ9 and (C) 3SJK between 3Cpro protein (gray color) with its targeted peptide (yellow color) (Lu et al., 2011). The figure was illustrated by Python-based Molecular View with a ribbon-shaped proteins or polypeptide and atom-shaped ligands.

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  FIGURE 4. Chemical structures of 21 ligands with five interacted chemical groups—showed in colored rectangles—and their interacted amino acids—showed in colored circles—at cluster 1 with 5C1U. The figure was modified from the illustration of BIOVIA Discovery Studio Visualizer v21.1.0.20298 (BIOVIA, 2021).

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  FIGURE 5. The average with standard deviation of docking scores (left) and the probability of models (right) at cluster 1—the active site—in each of 21 ligands and eight selected proteins. The shaded area was drawn based on the average docking score of all modal ligands at the active site with the 5C1U as a control. The significant difference was calculated by Kruskal–Wallis test and presented by different alphabets (α = 0.05) between each of eight proteins interacted with same ligand.

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  FIGURE 6. The number of clusters formed in docking each 21 ligands against each of eight proteins systems.

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  FIGURE 7. Percentage (upper) and average of docking scores (lower) of models bound at active site of each 29 ligands to eight different proteins. The vertical and horizontal dashed lines are the thresholds of the probability and the average of docking scores, respectively.

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  FIGURE 8. The stability of protein 5C1U and ligands through molecular dynamics simulation of two systems 5C1U-FIOMC and 5C1U-Hesperidin. The MD simulation was done with Gromacs version 2022.2 through 100 ns (Berendsen et al., 1995; van der Spoel et al., 2005; Abraham et al., 2015).