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

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.