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Research Article Open access CC BY 3.0

3D Structure Modeling of Human Telomere Repeat Binding Factor 2 and DNA-Protein Docking Studies

Koel Mukherjee, Dev Mani Pandey, Ambarish Saran Vidyarthi

Biotechnology Journal International · pp. 81–95 · Published 3 Dec 2013

10.9734/BBJ/2014/6381

Abstract

Aims: Human telomere repeat binding factor (hTRF2) is a double stranded telomere binding protein that plays key role in protecting the chromosome ends and a necessary building block of telomere structure maintenance. The aim of the present study was to focus on the modeling of 3D structure of hTRF2 (500 residues long) and its interaction studies with DNA in silico. Study Design: The overall work was designed in different steps starting with the modeling of the concerned protein, its physiochemical properties study, modeling of 3D-DNA with specific length and varying bend angle, docking studies of modeled DNA and hTRF2 protein. Place and Duration of Study: Bioinformatics Lab, Department of Biotechnology, Birla Institute of Technology, Mesra, India. November 2012- July 2013. Methodology: 3D structure of hTRF2 was modeled through I-TASSER method. The modeled structure was verified by 5ns of simulation run in solvent (water) condition and also evaluated with different bioinformatics tools. Physiochemical properties were calculated through CLC Protein Workbench.  DNA 3D structure was modeled with the conserved nucleotide sequence motif, TTAGGG with varying bend angles of 0° to 60°. The DNA-protein docking studies were carried out through HADDOCK easy interface for each bend angle. Results: The best model was selected depending on minimum RMSD value and C-Score and the Stereochemical quality of that model was verified with different tools, as the Molprobity score (>1) of hTRF2 was predicted 4.2 and Ramachandra favored residue was 80.56%. The selected model protein and DNA structure was docked and among all the docking results the best orientation of DNA and hTRF2 was at 60° DNA bend angle with lowest RMSD and maximum Z-value. The amino acids which are directly involved in the interaction were also selected. Conclusion: In future further study will be planned with further bend angle for getting better information on DNA-protein interactions. In silico studies will also be helpful for the researchers to study the complex structure in vitro.

DNA-protein docking ab initio modeling telomere binding protein transcription factors

References (42)

  1. 1 PROCHECK: a program to check the stereochemical quality of protein structures [DOI]
  2. 2 A simple method for displaying the hydropathic character of a protein [DOI]
  3. 3 GROMACS 3.0: a package for molecular simulation and trajectory analysis [DOI]
  4. 4 I-TASSER: a unified platform for automated protein structure and function prediction [DOI]
  5. 5 I-TASSER server for protein 3D structure prediction [DOI]
  6. 6 MolProbity: all-atom contacts and structure validation for proteins and nucleic acids [DOI]
  7. 7 Transcription factors: from enhancer binding to developmental control [DOI]
  8. 8 In Vivo Half-Life of a Protein Is a Function of Its Amino-Terminal Residue [DOI]
  9. 9 Force Fields for Protein Simulations [DOI]
  10. 10 ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins [DOI]
  11. 11 TRANSCRIPTION FACTORS: Structural Families and Principles of DNA Recognition [DOI]
  12. 12 The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter [DOI]
  13. 13 The HADDOCK web server for data-driven biomolecular docking [DOI]
  14. 14 TELOMERE LENGTH REGULATION [DOI]
  15. 15 The hydrophobic moment detects periodicity in protein hydrophobicity. [DOI]
  16. 16 Telomeres: Beginning to Understand the End [DOI]
  17. 17 Conservation of the human telomere sequence (TTAGGG)n among vertebrates. [DOI]
  18. 18 Telomeres and telomerase: their mechanisms of action and the effects of altering their functions [DOI]
  19. 19 Transcription factors: An overview [DOI]
  20. 20 LOMETS: A local meta-threading-server for protein structure prediction [DOI]
  21. 21 The many faces of the helix-turn-helix domain: Transcription regulation and beyond [DOI]
  22. 22 3D-DART: a DNA structure modelling server [DOI]
  23. 23 Information-driven protein-DNA docking using HADDOCK: it is a matter of flexibility [DOI]
  24. 24 In silico investigation of molecular mechanism of laminopathy caused by a point mutation (R482W) in lamin A/C protein [DOI]
  25. 25 Studies on Adaptability of Binding Residues Flap Region of TMC-114 Resistance HIV-1 Protease Mutants [DOI]
  26. 26 Protein–DNA contacts in the structure of a homeodomain–DNA complex determined by nuclear magnetic resonance spectroscopy in solution. [DOI]
  27. 27 The Crystal Structure of the DNA-Binding Domain of Yeast RAP1 in Complex with Telomeric DNA [DOI]
  28. 28 Comparison between TRF2 and TRF1 of their telomeric DNA‐bound structures and DNA‐binding activities [DOI]
  29. 29 Solution Structure of a Telomeric DNA Complex of Human TRF1 [DOI]
  30. 30 Cancer Associated E17K Mutation Causes Rapid Conformational Drift in AKT1 Pleckstrin Homology (PH) Domain [DOI]
  31. 31 Multiple sets of basal factors initiate transcription by RNA polymerase II [DOI]
  32. 32 Gene Regulation: A Eukaryotic Perspective
  33. 33 Sequence-specific DNA recognition by the Myb-like domain of the human telomere binding protein TRF1: A model for the protein-DNA complex [DOI]
  34. 34 Parametrization of GROMOS force field for oligosaccharides and assessment of efficiency of molecular dynamics simulations [DOI]
  35. 35 The orientation of the C-terminal domain of the Saccharomyces cerevisiae Rap1 protein is determined by its binding to DNA [DOI]
  36. 36 Structure of the DNA-binding domain of NgTRF1 reveals unique features of plant telomere-binding proteins [DOI]
  37. 37 Roadmap to determine the point mutations involved in cardiomyopathy disorder: A Bayesian approach [DOI]
  38. 38 Topological localization of the human transcription factors IIA, IIB, TATA box-binding protein, and RNA polymerase II-associated protein 30 on a class II promoter. [DOI]
  39. 39 Solution Structure of the DNA Binding Domain of Rice Telomere Binding Protein RTBP1, [DOI]
  40. 40 Structure of the DNA-binding domain of human telomeric protein, TRF1 and its interaction with telomeric DNA [DOI]
  41. 41 The general transcription factors of RNA polymerase II. [DOI]
  42. 42 Systematic functional characterization ofcis-regulatory motifs in human core promoters [DOI]

Cited by 4

In Silico Characterization and Analysis of RTBP1 and NgTRF1 Protein Through MD Simulation and Molecular Docking: A Comparative Study

K. Mukherjee, D. M. Pandey, A. S. Vidyarthi · Interdisciplinary Sciences Computational Life Sciences · 2015

In silico characterization and analysis of RTBP1 and NgTRF1 protein through MD simulation and molecular docking — A comparative study

Koel Mukherjee, Dev Mani Pandey, Ambarish Saran Vidyarthi · Interdisciplinary Sciences: Computational Life Sciences · 2015

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