title: Potential non homologous protein targets of mycobacterium tuberculosis H37Rv identified from protein-protein interaction network.
abstract: Bacillus mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis and H37Rv is the most studied strain. Identification of new drug targets for Mtb is among one of the priorities since it is still a major global health problem by being a cause of morbidity and mortality for millions of people each year. We used centrality measures to identify the most central proteins from protein-protein interaction network of mycobacterium tuberculosis H37Rv which was retrieved from STRING database by hypothesizing these proteins would be important to alter the function of the network. We then refined the result by using a dataset obtained from Drug Target Protein Database to identify non-human homologous proteins since in host-parasite diseases like tuberculosis; non-homologous proteins (enzymes) as drug target are the primary choices. We also tried to compare our proposed potential non-human homologous protein target lists against previously reported targets. Moreover, the structural coverage of the proposed target list has been identified. The analysis shows that 807 proteins in mycobacterium tuberculosis H37Rv were found at the center of gravity of the functional network of which 390 were non-human homologous, which are thought to be potential drug targets. 119 (30.51%) of the 390 proteins were reported as drug targets and only 33 (8.46%) of the non-human homologous proposed target lists have solved structure.
authors.affiliation: Department of Mathematics, IIT Roorkee, India. Electronic address: the_melak@yahoo.com.
authors.forename: Tilahun
authors.initials: T
authors.lastname: Melak
authors.affiliation: Department of Mathematics, IIT Roorkee, India. Electronic address: sungkfma@gmail.com.
authors.forename: Sunita
authors.initials: S
authors.lastname: Gakkhar
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D030562:Databases, Protein; D016503:Drug Delivery Systems; D054884:Host-Pathogen Interactions; D006801:Humans; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D014376:Tuberculosis / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins
keywords: Center of gravity; Centrality measures; Extensive drug resistant; Multi drug resistant; Total drug resistance