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Characterizing the pocketome of Mycobacterium tuberculosis and rationalization of polypharmacological target selection.
Identification of Binding Sites
Following illustration depicts the workflow involved in obtaining the binding sites at proteome level.
Following files contain the supporting information on the pocket predictions.
- Pocket_predictions.zip - This zipped file contains all the pocket predictions for the give protein structure. The pockets(denoted by r*[0-9].pdb) having overlap with LigsiteCSC and SiteHound predictions are flanked within the result folder named - 'cluster' for each protein. (Warning!: A huge file of 3 GB.)
- Consensus_pockets.zip - This zipped file contains PDB co-ordinates of all the pocket residues for the Mtb proteins structures.
- Literature_site_info_Mtbproteins.tsv - This file contains the information retried from literature on active/binding sites from Uniprot database using GFF(General Feature Format).
Genome-wide binding site comparisons
All the 13858 binding sites detected were subjected to pair-wise comparison using PocketMatch. Following are the results of the comparisons.
- PocketMatchComparisons.zip (Warning!: A huge file of ~2GB)
Binding Site Similarity Network and Clustering
Following files contain the information on binding site similarity network constructed.
- Mtb_within_significant_hits.csv - This file contains the information of significant similarity hits found within Mtb pocketome.
- MCODE_Mtbpocketome_results.txt - This file contains the MCODE clustering results for MtbPocketome.
Sequence-Structure-Pocket Comparisons
The raw file used to plot the 3D plot of sequence-structure-pocket relationship has been given below:
Drug and cofactor binding sites database
The information on drug-binding and cofactor-binding sites used in this study can be obtained from the following files:
Therapeutic Polypharmacological Index
All the computed therapeutic polypharmacological index for the pockets can be downloaded from these files.
- TPPI_Index.csv - This csv file contains the information on Therapeutic polypharmacology index for protein pockets within Mtb.
Validation
All the supporting files for validation section can be obtained from here.
- Mtb_proteins_SCOP_assignment.tsv - This tab separated file contains the SCOP assignment for the modeled proteins obatained using 3D-BLAST.
- Mtb_Proteins-Procognate_superpositions.zip - This zipped file contains all the superpositions of Mtb proteins with the corresponding proteins having same fold derived from PROCOGNATE database. The superpositions were generated using CLICK algorithm. (Warning!: A huge file of 8.3 GB.)
- Mtb_proteins_Ligand_association_PMScores.csv - This file contains all the ligand associations of Mtb proteins along with the information of the pocket that has matched and PocketMatch Scores.
- MOAD_sites_comparison_PMScores.tsv - This tab-separated file contains the pair-wise comparison results of the BindingMOAD sites with PM Scores.
- MCODE_Cluster_Results_MOAD_sites.txt - This file contains the result of MCODE clustering algorithm on binding-site similarity network obtained from MOAD all vs all comparison.
- MOAD_Binding_Site_Network.cys - This is a cytoscape session file displaying the binding-site similarity network obtained from BindingMOAD dataset. The nodes are colored according to their cluster. Please follow this link: http://wiki.cytoscape.org/GettingStarted for downloading Cytoscape and opening the session file.
- Average_tanimoto_scores_within_clusters.csv - This file contains the information on average tanimoto similarity scores obtained for all the ligands within each of the cluster detected.
- Mtb_targetTB_drug_association.tsv - This tab-serapated file contains the information of drug association with binding sites from high confidence targets derived from targetTB pipeline along with PocketMatch Scores.
- Mtb_Protein-Drug_docking.zip - This zipped file contains the docking poses for all the predicted drug assciations with the corresponding high-confidence targets. The docking was performed using AutoDock Vina.
- Drug_Scores.zip - This zipped file contains the scores for the native protein-drug complexes present in PDB.
- Mtb_relative_drug_association_scores.csv - This csv file contains the relative score of drug associations obtained through docking analysis.
Comparison to TB-Drugome
Following are the files containing supporting information for comparison agains TB-Drugome:
- TB-drugome_Pocket_overlap.csv - This csv file contains the information of overlap of pocket detected for protein models in TB-drugome against consensus analyses performed in this study.
- TB-drugome_PocketMatch_Scores.csv - This csv file contains the information of PocketMatch scores for the drug association reported by TB-Drugome study.
