Figure 1.
Structural scaffolds and Dock Scores of the top ten TCM compounds from TCM Database@Taiwan.
Candidate compounds investigated further in this study are highlighted with the dark green background in addition to the control compound Orlistat.
Figure 2.
Adsorption model of the candidate compounds.
Figure 3.
Docking poses of test ligands within PNLIP binding site.
(A) Aurantiamide, (B) cnidiadin,(C) 2-hexadecenoic acid, and (D) Orlistat. Residues on which interactions are formed are labeled in yellow. Green dash lines and red solid lines depict H-bonds and pi-interactions, respectively. Corresponding distances of the interactions are also given.
Figure 4.
Correlation between predicted and observed bioactivities (pIC50) using the (A) MLR and (B) SVM models.
Table 1.
Predicted pIC50 of top tenTCM ligands against PNLIP by MLR and SVM models.
Figure 5.
MD trajectories depicting changes during 40 ns simulation.
(A) Plot of complex RMSD, (B) plot of ligand RMSD, and (C) plot of complex total energy verses MD simulation time.
Figure 6.
Distance of H-bonds formed between test compounds and PNLIP binding site during MD.
(A) Aurantiamide, (B) Cnidiadin, (C) 2-hexadecenoic acid, and, (D) Orlistat.
Table 2.
H-bond interactions between PNLIP and top three candidates and Orlistat.
Figure 7.
Ligand interaction changes during MD.
Snapshots are taken for each test compound at 0 ns and 40 ns.
Figure 8.
Ligplot diagrams illustrating protein-ligand interactions.
(A) Aurantiamide, (B) Cnidiadin, (C) 2-Hexadecenoic acid, (D) Orlistat.
Figure 9.
Torsion angle changes during 40 ns MD simulation.
Each torsion angle is specified by a numerical and corresponds to the radar chart with the identical number. (A) Aurantiamide, (B) Cnidiadin, (C) 2-Hexadecenoic acid, (D) Orlistat.
Figure 10.
Secondary structure changes observed for binding cleft amino acid residues during the 40 ns MD simulation.
(A) Aurantiamide, (B) Cnidiadin, (C) 2-Hexadecenoic acid, (D) Orlistat.
Figure 11.
Top and side views of test compounds within the binding site following MD simulation.
(A) Aurantiamide, (B) Cnidiadin, (C) 2-Hexadecenoic acid, (D) Orlistat. (D) Orlistat. Residues involved in protein-ligand interactions are shown with pink surfaces, ligands are shown in yellow.
Figure 12.
Mean smallest residue distances for individual residues using 40 ns MD conformations.
Residues located in the active site cleft are shown in brackets within the enlarged illustration. (A) Aurantiamide, (B) Cnidiadin, (C) 2-Hexadecenoic acid, (D) Orlistat.
Figure 13.
Feature summary of the PNLIP binding site and TCM residues.
(A) PNLIP binding site consists of two parallel hydrophobic regions and several residues for pi-interactions as depicted by the violet rings. Amino acid legends are colored according to hydropathy. (B–D) Ligand features of (B) Aurantiamide, (C) Cnidiadin, and (D) 2-Hexadecenoic acid in coordination to binding site features are shown. Amino acids residues and ligand moieties forming hydrophobic contacts are shown in pink. Residues are moieties involved in pi-interaction are shown in violet. H-bonds are illustrated by yellow dashed lines.