Identification of membrane proteins as potential drug targets in Escherichia coli ATCC 25922 using in silico approaches

Koleiev, I. M.; Starosyla, S. A.; Protopopov, M. V.; Volynets, G. P.; Sapelkin, V. M.; Pletnova, L. V.; Syniugin, A. R.; Kachaput, N. O.; Matiushok, V. I.; Bdzhola, V. G.; Yarmoluk, S. M.

doi:10.7124/bc.000A38

Biopolym. Cell. 2020; 36(5):348-357.

http://dx.doi.org/10.7124/bc.000A38

Bioinformatics

Identification of membrane proteins as potential drug targets in Escherichia coli ATCC 25922 using in silico approaches

1Koleiev I. M., 2Starosyla S. A., 2Protopopov M. V., 2Volynets G. P., 2Sapelkin V. M., 2Pletnova L. V., 2Syniugin A. R., 2Kachaput N. O., 2, 3Matiushok V. I., 2Bdzhola V. G., 2Yarmoluk S. M.

Educational and Scientific Center "Institute of Biology and Medicine",
Taras Shevchenko National University of Kyiv
64/13, Volodymyrska Str., Kyiv, Ukraine, 01601
Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143
LLC “Scientific and service firm “Otava”
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143

Abstract

Aim. To identify the novel potential drug targets of E.coli ATCC 25922 through subtractive genomic analysis. Methods. The identification of non-homologous proteins to the human proteome, search for E.coli essential genes and estimation of drug target novelty were performed using BLAST. The unique metabolic pathways identification was done using the] data and tools from KEGG (Kyoto Encyclopedia of Genes and Genomes). Prediction of the sub-cellular proteins localization was performed using a combination of the tools PSORTb, CELLO and ngLOC. The homology modeling was performed by web-server I-TASSER, the models being validated using MolProbity web-server. The binding sites were analyzed using Discovery Studio 2017 with web servers ProBis and PrankWeb. Results. Proteome of Escherichia coli ATCC 25922, which contains 4808 proteins, has been taken to form the initial set. Using the subtractive genome analysis we identified 9 membrane proteins which are essential, non-homologous to human proteome, involved in unique metabolic pathways and are not described as [the] drug targets. A study of the spatial structure of this proteins showed that 6 of them have binding sites for ligands. Conclusions. Using classical bioinformatics approaches we identified 6 molecular targets of Escherichia coli ATCC 25922, which can be exploited for further rational drug design in order to find novel therapeutic agents for the treatment of infection caused by E.coli.

Keywords: Escherichia coli, antibiotic resistance, drug target, antibiotics, subtractive genomic analysis.

Full text: (PDF, in English)

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