Gaucher Disease: Task 05 - Homology Modelling
This page is still under construction.
Contents
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.