Identification of novel leads applying in silico studies for Mycobacterium multidrug resistant (MMR) protein

Abstract

Multidrug efflux mechanism is the main cause of intrinsic drug resistance in bacteria. Mycobacterium multidrug resistant (MMR) protein belongs to small multidrug resistant family proteins (SMR), causing multidrug resistance to proton (H⁺)-linked lipophilic cationic drug efflux across the cell membrane. In the present work, MMR is treated as a novel target to identify new molecular entities as inhibitors for drug resistance in Mycobacterium tuberculosis. In silico techniques are applied to evaluate the 3D structure of MMR protein. The putative amino acid residues present in the active site of MMR protein are predicted. Protein–ligand interactions are studied by docking cationic ligands transported by MMR protein. Virtual screening is carried out with an in-house library of small molecules against the grid created at the predicted active site residues in the MMR protein. Absorption distribution metabolism and elimination (ADME) properties of the molecules with best docking scores are predicted. The studies with cationic ligands and those of virtual screening are analysed for identification of new lead molecules as inhibitors for drug resistance caused by the MMR protein.

Keywords:

• multidrug efflux
• Mycobacterium tuberculosis
• small multidrug resistant protein family
• docking studies
• homology modeling

Acknowledgements

The author Dr. V. M. is grateful to University Grants Commission for the financial support through fellowship (UGC Major Research Project). The author Dr. S.R.P. acknowledges Department of Science and Technology, New Delhi for the financial support in pursuing the research work. The authors and Dr. V. M., K. K. M. and Dr. S.R.P. are thankful to the Principal, Nizam College, Osmania University for providing the facilities to carry out the work.