title: 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.
authors.affiliation: a Molecular Modelling Research Laboratory, Department of Chemistry , Nizam College, Osmania University , Basheerbagh, Hyderabad , Andhra Pradesh 500001 , India .
authors.forename: Vasavi
authors.initials: V
authors.lastname: Malkhed
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Mustyala
authors.forename: Sarita Rajender
authors.initials: SR
authors.lastname: Potlapally
authors.forename: Uma
authors.initials: U
authors.lastname: Vuruputuri
mesh_terms: D000595:Amino Acid Sequence; D000904:Antibiotics, Antitubercular / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D003198:Computer Simulation; D062126:Databases, Chemical; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011487:Protein Conformation; D054852:Small Molecule Libraries / Q000737:chemistry*
chemical_list: D000904:Antibiotics, Antitubercular; D001426:Bacterial Proteins; D008024:Ligands; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D054852:Small Molecule Libraries
keywords: Mycobacterium tuberculosis; docking studies; homology modeling; multidrug efflux; small multidrug resistant protein family