Fig 1.
Flow chart of this research process.
Table 1.
Collection of compounds and target genes for the study.
(a) shows the total count of KSK active compounds and total count of KSK similar compounds. There were 991 similar compounds in total in which 44 were removed for not having PubChem CIDs and 321 active compounds in total in which 23 were removed as they do not have PubChem CIDs. Totally 1,245 compounds were listed from which 38 duplicates were removed and 1,207 compounds were collected finally; (b) shows the number of target genes collected from TTD and NCBI databases.
Fig 2.
Construction of PPI network using STRING database.
(a) PPI Network of Total Target Genes. (b) Network Stats of the obtained result.
Table 2.
MCODE result shows 16 clusters score, number of nodes and edges, and node IDs.
Fig 3.
The final results are shown in cytoHubba.
(a) PPI Network of the top 10 hub genes. The red color indicates the nodes with high MCC scores, and the yellow indicates the node with a low MCC score. (b) Ranking of the top 10 hub genes using the MCC algorithm.
Fig 4.
Target-miRNA interaction network constructed in miRNet online tool.
Green nodes represent the target genes, and blue nodes represent miRNAs.
Table 3.
miRNAs of each hub genes given with the degree and the betweenness obtained from the miRNet tool.
Fig 5.
Gene Ontology Enrichment Analysis: Biological Process (BP), Cellular Component (CC) and Molecular Function (MF) were predicted for the given set of hub genes in the DAVID tool.
Fig 6.
Bubble plot of the pathway enrichment analysis (KEGG and Reactome pathways) and DisGeNET (information on other diseases associated with the hub genes) of the resultant hub genes using DAVID.
Fold Enrichment in the DAVID tool refers to the ratio of two proportions.
Fig 7.
Protein-ligand interaction analysis.
*First column shows the nonbonded interactions of the protein-ligand complexes where the ligand is represented as a ball and stick model and the protein predefined in the PLIP software; the distance between the interacted amino acid residues of the protein and the ligand is mentioned. The second column shows the hydrogen bond interactions in three-dimension using PyMOL where HBonds were measured, and without HBonds, the binding pocket was shown on the surface. The third column shows the hydrogen bond interactions in two-dimension using LigPlot+.
Table 4.
Binding affinity scores for top protein-ligand complexes.
Fig 8.
Compound-target-pathway network constructed in cytoscape.
*Ellipse-shaped nodes represent ten hub genes. Rectangle-shaped nodes represent the pathways involved by the genes. Triangle-shaped nodes represent the top nine compounds, and the dotted line represents the interaction between the nine compounds with the genes IFNG, IL10 and IL4.
Table 5.
Node specific statistics of network analyzer, given topological parameters for each hub gene.
Fig 9.
The RMSD plot of IL10 backbone and the ligand complexes.
a) RMSD results of IL10 and Guggulsterone; b) RMSD results of IL10 and Herkinorin; c) RMSD results of IL10 and mulberrofuran W.
Fig 10.
a) IL10 and Guggulsterone; b) IL10 and Herkinorin; c) IL10 and mulberrofuran W.