Modeling the interactions of herbal drugs to β-ketoacyl ACP synthase of Mycobacterium tuberculosis H37Rv

The present paper reports a bio-computational study carried out with the aim of understanding the binding mode of anti-TB herbal ligands onto the homology modeled structure of fatty acid synthase of Mycobacterium tuberculosis (M.tb) H37Rv. Sequence alignment of beta-ketoacyl ACP synthase (KAS) domain of the protein with other related KAS sequences of PDB database revealed high degree of sequence variation. However, the catalytic triad comprising of CHH (cys(150)-his(279)-his(320)) was found to be conserved in the KAS sequence of M.tb H37Rv. The tertiary structure of this protein predicted using genetic algorithm operator in the MODELLER package appeared to give a satisfactory structure for the purpose of studying ligand and substrate binding pockets on the protein. PDB templates complexed with ligands (citric acid and lauric acid) were used for model building, Docking studies carried out with different herbal ligands suggest that, aloe-emodin and nimbin are the best herbal candidates to replace the synthetic drugs 'thiolactomycin/cerulenin'.