Gaucher Disease: Task 05 - Homology Modelling

From Bioinformatikpedia
Revision as of 16:03, 11 June 2013 by Kalemanovm (talk | contribs)

This page is still under construction.

Calculation of models

Structures from task 04

We assembled the following structures in task 4, now we divide them into two groups: at > 60% and at < 30% sequence identity to our template protein, P04062 (536 aa long). PIDE was calculated as follows:

  • first we aligned the two fasta sequences from PDB with ClustalW
  • then calculated the PIDE (pairwise sequence identity) using SIAS with default options

Selected structures for modeling are written in bold.

Homologous structures to P04062
Structure PIDE with target Length
High PIDE
2XWD_A 91.51% 505 aa
2NSX_A 92.53% 497 aa
2NT1_A 92.53% 497 aa
Low PIDE
2GEP_A 10.74% 497 aa
2F7K_A 8.95% 327 aa
2QGU 5.59% 211 aa
2ISB_A 5.59% 192 aa
2DJF_A 3.17% 119 aa
2DJF_B 2.98% 164 aa
2DJF_C 4.47% 69 aa

As the PIDE with P04062 in the low-PIDE group we have selected in task 4 is too low and was not enough for Swissmodel to align the sequences, we looked again at the found hit list in task 2 (HHblits, 2 iterations against Uniprot20 followed by one iteration against pdb_full with E-value cutoff 10E-10). The set of structures finally used is:

Modeller - multiple target modeling

In multiple target modeling Modeller first aligns the user selected templates, then adds the target to the MSA, which is finally used for modeling. We tried the following template combinations:

  • several close homologues (> 60% sequence identity): 2XWD_A and 2NSX_A
  • several distant homologues (< 30% sequence identity): TODO (we had only very distant structures in our set)
  • one or more close and one or more distant homologues: TODO

Swissmodel

Model for 2GEP could not be created, because the alignment quality between target and specified template (2GEP) is too low and they could not be aligned with BLAST or HHsearch.

iTasser

The run with 2xwd as template is still running on the server.

For details how we executed the programs please see the lab journal.

Evaluation of models

Modeller

Swissmodel

iTasser