Prediction of Interactions between Mycobacterium tuberculosis Indole Glycerol Phosphate Synthase (IGPS) and Substrate Analogs

Tuberculosis (TB), which is the second most common cause of mortality worldwide, is caused by Mycobacterium tuberculosis (Mt). MtIGPS catalyzes the fourth step (transformation of 1-(o-carboxyphenylamino)-1-deoxyribulose 5’-phosphate (CdRP) into IGP) in the tryptophan biosynthetic pathway which is essential for M. tuberculosis growth. It over expresses the tryptophan pathway genes during an immune response and inhibition of MtIGPS allows CD4 T-cells to fight against M. tuberculosis more effectively therefore, MtIGPS could be a new potential drug target. Our goal is to computationally predict the binding of different compounds resembling CdRP to MtIGPS using molecular docking tools. Molecular docking is the prediction of interaction between protein and ligand using software. Consider a lock and key model in which the protein active site is the lock and various inhibitors are the keys to open this lock. For this purpose, the Maestro 13.4 version was used. It predicts types of interactions and binding energy (kcal/mol) for a ligand-MtIGPS pair. Using this program, protein (PDB ID: 3T44) and ligands were optimized using option “Protein preparation” and “Ligprep” respectively. A grid box was made around the active site to ensure docking will happen in that region only and Maestro displayed results in the form of binding energy and the poses of how ligands bind to MtIGPS. Our results show that Gly242 is an important interaction and removal of it can destabilize the protein-ligand complex and encourage further confirmation in the laboratory.