Subtractive Proteomic Approach for in Silico Identification and Characterization of Novel Drug Targets in Leishmania major.

摘要

The whole genome sequencing technology is providing expensive information for the identification of new therapeutic drug targets in pathogens. The availability of the complete proteome of Leishmania major has made it possible to carry out the in silico analysis of its proteome for identification of potential therapeutic targets. Our study revealed the essential proteins that are non-homologous to human genome and that are essential for the survival of the pathogen. The essentiality of the proteins of L. major was checked using the search against Database of Essential Genes (DEG). Subcellular localization prediction of these essential proteins was performed by CELLO server to find out proteins that lie on the outer membrane of the pathogen which could be potential drug targets. Metabolic pathway analysis of the identified essential surface proteins was performed using the KEGG Automated Annotation Server (KAAS) housed at KEGG pathways database. Comparative metabolic pathway analysis of H. sapiens and L. major was performed using KEGG database to find proteins involved in unique pathways of L.major. These essential proteins of L.major might be used as potential drug targets, as they belong to pathways present only in the pathogen and not in humans. Screening of the functional inhibitors against these novel targets may result in discovery of novel therapeutic compounds that can be effective against L.major. In present study subtractive genomic approach has been used to identify therapeutic target in L.major, which causes disfiguring cutaneous and muco-cutaneous lesions that can cause destruction of mucous membranes to visceral disease affecting the haemopoetic organs in humans.