PMID- 28740191
OWN - NLM
STAT- MEDLINE
DCOM- 20190410
LR  - 20200306
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jul 24
TI  - An in-silico glimpse into the pH dependent structural changes of T7 RNA 
      polymerase: a protein with simplicity.
PG  - 6290
LID - 10.1038/s41598-017-06586-1 [doi]
LID - 6290
AB  - 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.
FAU - Borkotoky, Subhomoi
AU  - Borkotoky S
AUID- ORCID: 0000-0001-6752-4296
AD  - Centre for Bioinformatics, School of Life Sciences, Pondicherry University, 
      Puducherry, 605014, India.
FAU - Kumar Meena, Chetan
AU  - Kumar Meena C
AD  - Centre for Bioinformatics, School of Life Sciences, Pondicherry University, 
      Puducherry, 605014, India.
FAU - Bhalerao, Gopalkrishna M
AU  - Bhalerao GM
AD  - UGC-DAE Consortium for Scientific Research Kalpakkam Node, Kokilamedu, Tamilnadu, 
      603104, India.
FAU - Murali, Ayaluru
AU  - Murali A
AUID- ORCID: 0000-0001-6406-6840
AD  - Centre for Bioinformatics, School of Life Sciences, Pondicherry University, 
      Puducherry, 605014, India. murali@bicpu.edu.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170724
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Viral Proteins)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9005-49-6 (Heparin)
RN  - EC 2.7.7.- (bacteriophage T7 RNA polymerase)
RN  - EC 2.7.7.6 (DNA-Directed RNA Polymerases)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Computational Biology/*methods
MH  - *Computer Simulation
MH  - DNA-Directed RNA Polymerases/*chemistry/*metabolism
MH  - Heparin/metabolism
MH  - Hydrogen-Ion Concentration
MH  - *Molecular Docking Simulation
MH  - *Molecular Dynamics Simulation
MH  - Protein Conformation
MH  - Viral Proteins/*chemistry/*metabolism
PMC - PMC5524818
COIS- The authors declare that they have no competing interests.
EDAT- 2017/07/26 06:00
MHDA- 2019/04/11 06:00
PMCR- 2017/07/24
CRDT- 2017/07/26 06:00
PHST- 2017/01/17 00:00 [received]
PHST- 2017/06/14 00:00 [accepted]
PHST- 2017/07/26 06:00 [entrez]
PHST- 2017/07/26 06:00 [pubmed]
PHST- 2019/04/11 06:00 [medline]
PHST- 2017/07/24 00:00 [pmc-release]
AID - 10.1038/s41598-017-06586-1 [pii]
AID - 6586 [pii]
AID - 10.1038/s41598-017-06586-1 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jul 24;7(1):6290. doi: 10.1038/s41598-017-06586-1.