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Modeling of Alternate RNA Polymerase Sigma D Factor and Identification of Novel Inhibitors by Virtual Screening

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Abstract

Tuberculosis is one of the deadliest threats to public health and is the cause of 2 million deaths with increasing number every year. The ability of Mycobacterium tuberculosis pathogen to adapt to intracellular stress needs regulation of complex gene expression mediated mainly by sigma factors. Sigma factors of Mycobacterium are RNA polymerase subunits; confer the DNA binding at specific promoter and aid in transcription initiation. The structure of probable RNA polymerase Sigma D factor protein, with 221 amino acid residues, was evaluated by applying comparative modeling (homology) techniques-considering RNA polymerase Sigma E factor of E. coli (PDB ID: 1OR7) as template. The 3D model generated is validated and active site cleft was identified. Lead molecules were identified by applying virtual screening studies using National cancer institute open database. The in silico ADME prediction revealed a set of novel inhibitor molecules targeting the Sigma D protein. The present studies help in identification of selective potent inhibitors which are safe and can act as anti-tuberculosis agents.

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Acknowledgments

The author Dr. V. M. is thankful to the University Grants Commission, New Delhi for the financial support for carrying out this work under the major research project scheme (UGC Project F. No. 34-302/2008(SR), dated: 24/12/2008). The author Dr. S. R. P. acknowledges the Department of Science and Technology (DST) for the financial support in pursuing the research work. The authors Dr. V. M., K. K. M. and Dr. S. R. P. thank the Head Department of Chemistry and the Principal, Nizam College for providing the facilities to carry out the work.

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  1. Department of Chemistry, Nizam College, Osmania University, Basheerbagh, Hyderabad, 500001, Andhra Pradesh, India

    Vasavi Malkhed, Kiran Kumar Mustyala, Sarita Rajender Potlapally & Uma Vuruputuri

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  1. Vasavi Malkhed
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Correspondence to Uma Vuruputuri.

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Associate Editor David J. Odde oversaw the review of this article.

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Malkhed, V., Mustyala, K.K., Potlapally, S.R. et al. Modeling of Alternate RNA Polymerase Sigma D Factor and Identification of Novel Inhibitors by Virtual Screening. Cel. Mol. Bioeng. 5, 363–374 (2012). https://doi.org/10.1007/s12195-012-0238-7

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