Additional file 1: Table S1. KEGG pathways for genes known to be
associated with 1st and 2nd line drug resistance. The 10 mutations (eight
genes) indicated in bold were verified by the BROAD institute, while the
remainder were identified from literature. Abbreviations used: A-Adenine,
Ala-Alanine, Arg-Arginine, Asn-Glutamine, Asp-Aspartate, Gly-Glycine,
His-Histidine, indel-insertion deletion, Ileu-Isoleucine, Leu-Leucine,
Met-Methionine, N.A-Not available, Pro-Proline, Ser-Serine, T-Thymidine,
Thr-Threonine, Tyr-Tyrosine, Val-Valine. (PDF 143 kb)
Additional file 2: Table S2. Criteria used to filter high priority
M.tuberculosis drug targets. The genes highlighted in bold satisfied all the
selection criteria. The hyphen (−) indicates exclusion from further analysis.
Abbreviations used: NUI- Not under investigation, PDB- Protein Data Bank,
TBSGC- TB Structural Genome Consortium. References 12-Sassetti et al., 2003;
34-Lamichhane et al., 2003. Data can be viewed in Microsoft excel. (XLS 12 kb)
Additional file 3: Table S3. The 24 sequenced Mycobacterium strains.
Data can be viewed in Microsoft excel. (XLS 34 kb)
Additional file 4: Table S4. Blast hits obtained for Rv1712, Rv2984, Rv2194,
Rv1311, Rv1305, Rv2195, Rv1622c, Rv1456c and Rv2421c against three host
intestinal bacteria. Bacterial species highlighted in bold showed homology to
the query gene. Data can be viewed in Microsoft excel. (XLS 13 kb)
Additional file 5: Figure S1. KEGG metabolic pathway map for
Nucleotide metabolism (pyrimidine metabolism) in M. tuberculosis
H37rV strain. Rv1712 or cmk selected for investigation is shown in red
highlighted boxes and involved in step 2.7.4.14 of this specific pathway.
Known drug resistance gene Rv0667 or rpoB is shown in blue highlighted
box and involved in step 2.7.7.6 of this pathway. M. tuberculosis specific
genes are coloured in green. (PDF 111 kb)
Additional file 6: Figure S2. KEGG metabolic pathway map for Oxidative
phosphorylation in M. tuberculosis H37rV strain. Rv2984 or ppk selected for
investigation is shown in blue highlighted box and involved in step 2.7.4.1
of this specific pathway. Rv2194 or qcrC selected for investigation is shown
in the red highlighted box. Both Rv1305 (atpE) and Rv1311 (atpC) selected
for investigation are shown in brown highlighted box and involved in step
3.6.3.14 of this specific pathway. Rv2195 or qcrA selected for investigation is
shown in the yellow highlighted box involved in cytochrome C reductase.
Rv1456c or COX15 selected for investigation is shown in the magenta
highlighted box involved in cytochrome C oxidase. Rv1622c or CydB
selected for investigation is shown in the light blue highlighted box
involved in cytochrome C oxidase. Known drug resistance gene Rv1854c or
ndh is shown in orange highlighted box and involved in step 1.6.99.3 of this
pathway. M. tuberculosis specific genes are coloured in green. (PDF 157 kb)
Additional file 7: Figure S3. KEGG metabolic pathway map for
Nicotinate and Nicotinamide metabolism in M. tuberculosis H37rV strain.
Rv2421c or nadD selected for investigation is shown in red highlighted
box and involved in step 2.7.7.18 of this specific pathway. Known drug
resistance gene Rv2043c or pncA is shown in blue highlighted box and
involved in step 3.5.1.19 of this pathway. M. tuberculosis specific genes
are coloured in green. (PDF 106 kb)
Additional file 8: Table S5. KEGG pathway descriptors for M.
tuberculosis genes retained after prioritization. Data can be viewed in
Microsoft excel. (XLS 7 kb)
Additional file 9: Figure S4. DOPE score energy profiles graph of the
structural model for Rv1712 (red) and templates 1Q3T (green), 1CKE (dark
blue), 1KDO (light blue) and 2H92 (purple). Generated using Gnuplotv4.2
[41]. (PDF 68 kb)
Additional file 10: Figure S5. RMSD of the backbone atoms of model
Rv1712 (green) and substrate C5P (red) during the 30000 ps simulation.
Generated using Gnuplotv4.2 [41]. (PDF 198 kb)
Additional file 11: Figure S6. The variation in total (green) and
potential energy (red) for the Rv1712-C5P complex during the 30000 ps
simulation. Generated using Gnuplotv4.2 [41]. (PDF 69 kb)
Additional file 12: Figure S7. RMS fluctuations of all Cα residues for
Rv1712 over the 30000 ps simulation. (PDF 55 kb)
Additional file 13: Figure S8. Radius of gyration of all bacbone atoms
for Rv1712 over the 30000 ps simulation. (PDF 29 kb)
Additional file 14: Figure S9. Superimposition of lowest DOPE score
models for the initial and newly generated structures. The blue model
represents the initial model without 3R20 used as a template while the
red model consist of 3R20 used as a template for model construction.
Ligands SO4 and CMP are shown as sticks. RMSD = 0.387 Å. (PDF 33 kb)
Additional file 15: Table S6. Docking scores and number of
interactions for the top ten compounds to Rv1712. The residues
highlighted in bold are conserved catalytic residues while ligand C5P is
highlighted in red. The numbers inside the () indicate the number of
interactions formed between residue and the compound atom. Data can
be viewed in Microsoft excel. (XLS 8 kb)