An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity

Abstract The capability of performing an array of functions with its single subunit structure makes T7 RNA polymerase (T7RNAP) as one of the simplest yet attractive target for various investigations ranging from structure determinations to several biological tests. In this study, with the help of mo...

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Autores principales:	Subhomoi Borkotoky, Chetan Kumar Meena, Gopalkrishna M. Bhalerao, Ayaluru Murali
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a43eeeb9977b4f618bb956a8feffbd76
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spelling	oai:doaj.org-article:a43eeeb9977b4f618bb956a8feffbd762021-12-02T15:05:26ZAn in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity10.1038/s41598-017-06586-12045-2322https://doaj.org/article/a43eeeb9977b4f618bb956a8feffbd762017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06586-1https://doaj.org/toc/2045-2322Abstract The capability of performing an array of functions with its single subunit structure makes T7 RNA polymerase (T7RNAP) as one of the simplest yet attractive target for various investigations ranging from structure determinations to several biological tests. In this study, with the help of molecular dynamics (MD) calculations and molecular docking, we investigated the effect of varying pH conditions on conformational flexibility of T7RNAP. We also studied its effect on the interactions with a well established inhibitor (heparin), substrate GTP and T7 promoter of T7RNAP. The simulation studies were validated with the help of three dimensional reconstructions of the polymerase at different pH environments using transmission electron microscopy and single particle analysis. On comparing the simulated structures, it was observed that the structure of T7RNAP changes considerably and interactions with its binding partners also changes as the pH shifts from basic to acidic. Further, it was observed that the C-terminal end plays a vital role in the inefficiency of the polymerase at low pH. Thus, this in-silico study may provide a significant insight into the structural investigations on T7RNAP as well as in designing potent inhibitors against it in varying pH environments.Subhomoi BorkotokyChetan Kumar MeenaGopalkrishna M. BhaleraoAyaluru MuraliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Subhomoi Borkotoky Chetan Kumar Meena Gopalkrishna M. Bhalerao Ayaluru Murali An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity
description	Abstract The capability of performing an array of functions with its single subunit structure makes T7 RNA polymerase (T7RNAP) as one of the simplest yet attractive target for various investigations ranging from structure determinations to several biological tests. In this study, with the help of molecular dynamics (MD) calculations and molecular docking, we investigated the effect of varying pH conditions on conformational flexibility of T7RNAP. We also studied its effect on the interactions with a well established inhibitor (heparin), substrate GTP and T7 promoter of T7RNAP. The simulation studies were validated with the help of three dimensional reconstructions of the polymerase at different pH environments using transmission electron microscopy and single particle analysis. On comparing the simulated structures, it was observed that the structure of T7RNAP changes considerably and interactions with its binding partners also changes as the pH shifts from basic to acidic. Further, it was observed that the C-terminal end plays a vital role in the inefficiency of the polymerase at low pH. Thus, this in-silico study may provide a significant insight into the structural investigations on T7RNAP as well as in designing potent inhibitors against it in varying pH environments.
format	article
author	Subhomoi Borkotoky Chetan Kumar Meena Gopalkrishna M. Bhalerao Ayaluru Murali
author_facet	Subhomoi Borkotoky Chetan Kumar Meena Gopalkrishna M. Bhalerao Ayaluru Murali
author_sort	Subhomoi Borkotoky
title	An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity
title_short	An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity
title_full	An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity
title_fullStr	An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity
title_full_unstemmed	An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity
title_sort	in-silico glimpse into the ph dependent structural changes of t7 rna polymerase: a protein with simplicity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a43eeeb9977b4f618bb956a8feffbd76
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An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity

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