Structure prediction of drug target identified by metabolic pathway analysis of Streptococcus pyogenes

Target identification is the first step in the drug and vaccine discovery process, in silico subtractive genomics is widely used in this process. We used this in silico approach for identification of essential proteins in Streptococcus pyogenes strain M1, a Gram-positive bacterium, which is an important human pathogen. S. pyogenes causes wide variety of disease, including pharyngitis (streptococcal sore throat), scarlet fever, impetigo, erysipelas, cellulitis, septicemia, toxic shock syndrome, necrotizing fasciitis (flesh-eating disease) and the sequelae, rheumatic fever and acute glomerulonephritis in humans. Further, using the KEGG Automatic Annotation Server, we identified six unique metabolic pathways that exist in this bacterium but not in human and some essential S. pyogenes proteins that are involved in these bacterial pathways. Analysis using CELLO, showed that essential S. pyogenes strain M1 proteins were membrane proteins and thus more amenable as drug targets. Therefore, based on identification, six drug target have been identified and their genes: SPy_1283, SPy_0890, SPy_0399, SPy_1849, SPy_1652, SPy_1233 whereas homology modeling for 6-phosphofructokinase were performed for inhibitor designing. This work has a lot of potential in research work for development of strategies for control and treatment of S. pyogenes, including targets that have been identified with this technique and various other aspects.