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Fig 1.

Methodology flowchart.

pLDDT, predicted local distance difference test; PAE, predicted aligned error; flDPnn, putative function- and linker-based Disorder Prediction using deep neural network.

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Fig 1 Expand

Fig 2.

Evaluation of EtfD’s predicted structure.

(a) EtfD’s structure colored by pLDDT scores, with red indicating high confidence and blue indicating low confidence. The cartoon representation is overlaid with a semi-transparent surface. (b) pLDDT score plot.

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Fig 3.

EtfD’s ligand binding site analysis.

(a) The overall protein structure is shown in blue as a cartoon, with the surface displayed. Binding site residues are highlighted in red and shown as balls. (b) Close-up view of the binding site. (c) Ligand binding site residues with their corresponding residue specific probabilities, as predicted by the COACH metaserver. (d) Predicted interactions between the ligand SF4 and binding site residues. Hydrogen bonds are shown in olive green, iron-sulfur coordinate bonds in purple, carbon in black, nitrogen in blue, oxygen in red, sulfur in yellow, and iron in pink. Hydrophobic interactions are not shown to avoid obscuring details, but the names of the residues involved in hydrophobic interactions are labeled in black.

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Fig 4.

Molecular models showing binding interactions between EtfD and diacerein, levonadifloxacin, and gatifloxacin in 3D and 2D.

(a and b) EtfD-diacerein, (c and d) EtfD-levonadifloxacin, (e and f) EtfD-gatifloxacin. EtfD hydrogen-bonding residues are shown as sticks (carbon: green, nitrogen: blue, oxygen: red), with hydrogen bonds represented by red dashed lines. 2D interaction diagrams follow the same color scheme as described in Fig 3d. Common amino acids involved in interactions with EtfD across diacerein, levonadifloxacin, and gatifloxacin are ARG133, ARG146, ALA155, HIS235, and CYS298.

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Table 1.

Binding affinity scores for top 20 drug molecules (AutoDock4).

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Fig 5.

Investigating the stability of EtfD-drug complexes through MD simulations using various statistical parameters.

(a) RMSD. (b) RMSF. (c) RoG. (d) hydrogen bonding. RMSD, root mean square deviation; RMSF, root mean square fluctuation; RoG, radius of gyration.

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Table 2.

MM-G/PBSA net binding energy of the molecules presented for each energy component.

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Table 3.

Predicted druglikeness and ADMET analysis of the compounds.

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Table 4.

Anti-TB activity prediction of top drugs through online server mycoCSM.

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