in silico analyses of metabolic pathway and protein interaction network for identification of next gen therapeutic targets in Chlamydophila pneumoniae

Bioinformation. 2013 Jul 12;9(12):605-9. doi: 10.6026/97320630009605. Print 2013.

Abstract

Chlamydophila pneumoniae, the causative agent of chronic obstructive pulmonary disease (COPD), is presently the fifth mortality causing chronic disease in the world. The understanding of disease and treatment options are limited represents a severe concern and a need for better therapeutics. With the advancements in the field of complete genome sequencing and computational approaches development have lead to metabolic pathway analysis and protein-protein interaction network which provides vital evidence to the protein function and has been appropriate to the fields such as systems biology and drug discovery. Protein interaction network analysis allows us to predict the most potential drug targets among large number of the non-homologous proteins involved in the unique metabolic pathway. A computational comparative metabolic pathway analysis of the host H. sapiens and the pathogen C pneumoniae AR39 has been carried out at three level analyses. Firstly, metabolic pathway analysis was performed to identify unique metabolic pathways and non-homologous proteins were identified. Secondly, essentiality of the proteins was checked, where these proteins contribute to the growth and survival of the organism. Finally these proteins were further subjected to predict protein interaction networks. Among the total 65 pathways in the C pneumoniae AR39 genome 10 were identified as the unique metabolic pathways which were not found in the human host, 32 enzymes were predicted as essential and these proteins were considered for protein interaction analysis, later using various criteria's we have narrowed down to prioritize ribonucleotide-diphosphate reductase subunit beta as a potential drug target which facilitate for the successful entry into drug designing.

Keywords: COPD; Chlamydophila pneumoniae; Protein interaction network analysis; computational approaches; metabolic pathway analysis.