Bharathkumar Inturi
JSS College of Pharamcy India
Title: PROTEIN LIGAND BASED PHARMACOPHORE MODELING: A SEARCH FOR NOVEL MYCOBACTERIUM TUBERCULOSIS InhA INHIBITORS
Biography
Biography: Bharathkumar Inturi
Abstract
Mycobacterium tuberculosis responsible for nearly two million deaths each year[1], the infectious disease tuberculosis remains a serious global health challenge. The emergence of multidrug- and extensively drug-resistant strains of mtb confounds control efforts, and new drugs with novel molecular targeting approaches are desperately needed. The current study describes the use of protein−ligand-derived pharmacophore model as a tool to identify the novel Mtb InhA inhibitors. The pharmacophore model was generated considering the ligand, hydrogen bonding interactions and active site of targeted protein. We have developed a three feature pharmacophore model consisting donor, hydrophobic and aromatic features by considering the co-crystallized ligand of InhA(Fig-1A) (PDB:3FNG)[2] and also hydrogen bond interactions(Fig-1B) and active site of the co- crystallized ligand(Fig-1C).This model was used to search the database of 200,000 molecules. Best 5000 hits was considered for molecular docking approach, from the docking results, top hits were further considered for the molecular dynamic study to find the stability of protein ligand interaction stability. Based on dynamic results best 5 molecules were synthesized and the evaluation is under progress against mtb H37Rv.