CELL2007 Molecular Exploration Project
Group 7
Secondary Structure Prediction
PHYRE2
PHYRE uses PSI-BLAST to initally scan the FASTA sequence and then runs the results from this through PSIPRED to create a secondary structure prediction profile. It also runs this information through DISOPRED to predict regions of disorder.
The PHYRE analysis of TESK1 predicted the following:
Disordered: 57%
Alpha helix: 21%
Beta Strand: 9%
Transmembrane helix: 3%
The region with highest confidence levels and density of helices and sheets, corresponds to around 40-330 residues. This region roughly corresponds to kinase domain of TESK1, as shown in the NCBI protein graphics diagram below.
The accuracy of prediction by this software is generally rather limited. This most likely accounts for large proportion of disordered regions.
Figure 6: Adapted from the results of a PHYRE2 analysis.
[2] Protein structure prediction on the web: a case study using the Phyre server
Kelley LA and Sternberg MJE. Nature Protocols 4, 363 - 371 (2009)
Figure 7: Graphical display of TESK1 and constituent domains. Adapted from: NCBI website proteins search tool. Available from link attached to figure [3].
Kyte-Doolittle
Kyte-Doolittle is a quantitative analytical tool used to predict the the degree of hydrophobicity of a given amino acid sequence. This can then be used to predict possible structural features or indicate the presence of certain domains.
The plot generated from the TESK1 FASTA sequence indicates that the proteins has a greater number of hydrophilic residues. These are most likely distributed on the surface of the proteins and interact with the cytosol. TESK1 is therefore most likely to be cytosolic, and this assumption corresponds to information known about TESK1's interaction within the cell.
Figure 8: Hydropathy plot of TESK1 generated using Kyte-Doolittle.
[4] Kyte, J. and Doolittle, R. 1982. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157: 105-132.