European Journal of Biomedical and Pharmaceutical Sciences

IN SILICO IDENTIFICATION AND CHARACTERIZATION OF POTENTIAL DRUG TARGETS IN HUMAN PATHOGEN SHIGELLA FLEXNERI

*Desai Sharav and Meshram Dhananjay

ABSTRACT

Shigellosis is a significant cause of morbidity and mortality in children amongst developing countries. Newly emerging Antibiotic-resistant strains from all over the world are also one of the alarming conditions in the treatment and management of infection clinically. Such conditions calls for immediate investigation of all available proteins in the species that can act as a target for controlling the disease. The traditional discovery process can result in an enormous amount of time with effort. In the present work novel in-silico ordered approach is used to identify and characterize potential drug target in Shigella flexneri species. Three phase of analysis used to screen proteins in the species and at every phase, the proteins were filtered according to define parameters. In phase, I proteins from five sets (Chokepoint, Pathway, Plasmid, Virulence, and resistant) collected from described sources. Total of 1,276 proteins resulted from the phase I analysis. Phase II studies resulted in 220 proteins with several of target characteristics. Phase III studies led to a final list of three proteins namely CytidylateKinase, Ribunuclease and 2-amino-4-hydroxy-6-hydroxymethyl dihydro pteridine pyrophosphokinase. Protein homology modeling and structure refinement studies produced five models for each of the target. ERRAT profile, QMEAN6, Z-Score and distribution of residues using Ramachandran plot were considered as parameters of validation. Structures were analyzed for normal mode analysis using the Bio3D package in R to promote molecular dynamic studies. Proteins resulted can be developed as a potential drug target for infections occurring by Shigella flexneri.

Keywords: Computer Simulation, Drug Resistance, Gastrointestinal Microbiota In Silico Models, Protein Interaction Maps, Protein Sequence Analysis, Virulence Factors.