Difference between revisions of "Homology modelling TSD"

From Bioinformatikpedia
(→‎Evaluation)
(→‎Templates)
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== Templates ==
  
== Templates ==
   
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Since similar sets were already collected for [[Sequence_Alignments_TSD#Dataset_creation|Task 2]], the information was reused. In addition searches with HHpred on pdb70 and with COMA on pdb40 were performed. If two structures were mapped to the same Uniprot entry, only one, the 'most native' one, was used.
 +
Since similar sets were already collected for [[Sequence_Alignments_TSD#Dataset_creation|Task 2]], the information was reused. In addition searches with HHpred on pdb70 and with COMA on pdb40 were performed. If two structures were mapped to the same Uniprot entry, only one, the 'most native' one, was used. The set of chosen templates is displayed in <xr id="tab:templates" />.
 
<br/>
  
<br/>
 
None of the searches revealed any structure with >80% sequence identity, other than the two already known structures 2gjx and 2gk1 which share 100% sequence identity. To still perform the task, 2gjx, which is the native structure <ref name="2gjxref">Lemieux,M. et al. (2006) Crystallographic Structure of Human beta-Hexosaminidase A: Interpretation of Tay-Sachs Mutations and Loss of GM2 Ganglioside Hydrolysis. Journal of molecular biology, 359, 913-29.</ref>, was chosen as reference and 2gk1, which has the inhibitor NGT bound, will be used as template. In the range between 40/80% sequence identity only one entry could be added from COMA. Most of the hits found by either COMA or HHpred turned out to have a sequence identity of lower than 25%.
  
None of the searches revealed any structure with >80% sequence identity, other than the two already known structures 2gjx and 2gk1 which share 100% sequence identity. To still perform the task, 2gjx, which is the native structure <ref name="2gjxref">Lemieux,M. et al. (2006) Crystallographic Structure of Human beta-Hexosaminidase A: Interpretation of Tay-Sachs Mutations and Loss of GM2 Ganglioside Hydrolysis. Journal of molecular biology, 359, 913-29.</ref>, was chosen as reference and 2gk1, which has the inhibitor NGT bound, will be used as template. In the range between 40/80% sequence identity only one entry could be added from COMA. Most of the hits found by either COMA or HHpred turned out to have a sequence identity of lower than 25%.
   
 
<!-- Nur eine vorläufige tabelle-->
  
<!-- Nur eine vorläufige tabelle-->
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<figtable id="tab:signals">
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<figtable id="tab:templates">
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{| class="wikitable", style="width:550px; border-collapse: collapse; border-style: solid; border-width:0px; border-color: #000"
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{| class="wikitable", style="width:650px; border-collapse: collapse; border-style: solid; border-width:0px; border-color: #000"
 
|-align="left"
  
|-align="left"
 
! style="border-style: solid; border-width: 0 0 2px 0" |
 
! style="border-style: solid; border-width: 0 0 2px 0" |
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|-
  
|-
 
! style="border-style: solid; border-width: 0 0 0 0" align="left" rowspan="1" | > 80% identity
  
! style="border-style: solid; border-width: 0 0 0 0" align="left" rowspan="1" | > 80% identity
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| style="border-style: solid; border-width: 0 0 0 0" | 2gk1
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| style="border-style: solid; border-width: 0 0 0 0" | [http://www.pdb.org/pdb/search/structidSearch.do?structureId=2gk1 2gk1] chain A
 
| style="border-style: solid; border-width: 0 0 0 0" | 100%
  
| style="border-style: solid; border-width: 0 0 0 0" | 100%
 
| style="border-style: solid; border-width: 0 0 0 0" | Task2/HHpred/COMA
  
| style="border-style: solid; border-width: 0 0 0 0" | Task2/HHpred/COMA
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|-
  
|-
 
! style="border-style: solid; border-width: 0 0 0 0" align="left" rowspan="2" | 40% - 80% identity
  
! style="border-style: solid; border-width: 0 0 0 0" align="left" rowspan="2" | 40% - 80% identity
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| style="border-style: solid; border-width: 0 0 0 0" | 1o7a_D
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| style="border-style: solid; border-width: 0 0 0 0" | [http://www.pdb.org/pdb/search/structidSearch.do?structureId=1o7a 1o7a] chain D
 
| style="border-style: solid; border-width: 0 0 0 0" | 56.6%
  
| style="border-style: solid; border-width: 0 0 0 0" | 56.6%
 
| style="border-style: solid; border-width: 0 0 0 0" | Task 2
  
| style="border-style: solid; border-width: 0 0 0 0" | Task 2
 
|-
  
|-
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| style="border-style: solid; border-width: 0 0 0 0" | 3lmy_A
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| style="border-style: solid; border-width: 0 0 0 0" | [http://www.pdb.org/pdb/search/structidSearch.do?structureId=3lmy 3lmy] chain A
 
| style="border-style: solid; border-width: 0 0 0 0" | 54%
  
| style="border-style: solid; border-width: 0 0 0 0" | 54%
 
| style="border-style: solid; border-width: 0 0 0 0" | COMA
  
| style="border-style: solid; border-width: 0 0 0 0" | COMA
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|-
  
|-
 
! style="border-style: solid; border-width: 0 0 0 0" align="left" rowspan="3" | < 30% identity
  
! style="border-style: solid; border-width: 0 0 0 0" align="left" rowspan="3" | < 30% identity
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| style="border-style: solid; border-width: 0 0 0 0" | 3nsm_A
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| style="border-style: solid; border-width: 0 0 0 0" | [http://www.pdb.org/pdb/search/structidSearch.do?structureId=3nsm 3nsm] chain A
 
| style="border-style: solid; border-width: 0 0 0 0" | 27.5%
  
| style="border-style: solid; border-width: 0 0 0 0" | 27.5%
 
| style="border-style: solid; border-width: 0 0 0 0" | Task 2
  
| style="border-style: solid; border-width: 0 0 0 0" | Task 2
 
|-
  
|-
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| style="border-style: solid; border-width: 0 0 0 0" | 3gh5_A
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| style="border-style: solid; border-width: 0 0 0 0" | [http://www.pdb.org/pdb/search/structidSearch.do?structureId=3gh5 3gh5] chain A
 
| style="border-style: solid; border-width: 0 0 0 0" | 20.7%
  
| style="border-style: solid; border-width: 0 0 0 0" | 20.7%
 
| style="border-style: solid; border-width: 0 0 0 0" | Task 2
  
| style="border-style: solid; border-width: 0 0 0 0" | Task 2

Revision as of 15:19, 1 June 2012

There will be no curiosity, no enjoyment of the process of life. All competing pleasures will be destroyed. But always — do not forget this, Winston — always there will be the intoxication of power, constantly increasing and constantly growing subtler. Always, at every moment, there will be the thrill of victory, the sensation of trampling on an enemy who is helpless. If you want a picture of the future, imagine a boot stamping on a human face — forever.

1984


protocol

Templates

Since similar sets were already collected for Task 2, the information was reused. In addition searches with HHpred on pdb70 and with COMA on pdb40 were performed. If two structures were mapped to the same Uniprot entry, only one, the 'most native' one, was used. The set of chosen templates is displayed in <xr id="tab:templates" />.
None of the searches revealed any structure with >80% sequence identity, other than the two already known structures 2gjx and 2gk1 which share 100% sequence identity. To still perform the task, 2gjx, which is the native structure <ref name="2gjxref">Lemieux,M. et al. (2006) Crystallographic Structure of Human beta-Hexosaminidase A: Interpretation of Tay-Sachs Mutations and Loss of GM2 Ganglioside Hydrolysis. Journal of molecular biology, 359, 913-29.</ref>, was chosen as reference and 2gk1, which has the inhibitor NGT bound, will be used as template. In the range between 40/80% sequence identity only one entry could be added from COMA. Most of the hits found by either COMA or HHpred turned out to have a sequence identity of lower than 25%.

<figtable id="tab:templates">

PDB id Sequence identity Method
> 80% identity 2gk1 chain A 100% Task2/HHpred/COMA
40% - 80% identity 1o7a chain D 56.6% Task 2
3lmy chain A 54% COMA
< 30% identity 3nsm chain A 27.5% Task 2
3gh5 chain A 20.7% Task 2

Table TODO: </figtable>


Alignments

SWISS-MODEL

Default Modelling


Chosen template 2gjx_E.

High sequence identity

Medium Sequence identity

Low sequence identity

With the 3gh5 as template the automated SWISS-MODEL was not able to calculate a model structure for the Hex A subunit. Two alignments were produced, one with Blast and one with HHsearch. While the Blast alignment quality between target and template was too low to start with, the HHsearch alignment reached the next level and was sent to modelling but the building of a model was not successful.
The same occured for 3nsm which has a sequence identity about 7% higher than 3gh5. A sequence identity lower than 30% seems to be too low for modelling.

Evaluation

<figtable id="tab:swisseval">

Residues in common Common residue RMSD TM GDT-TS GDT-HA
Default 492 0.573 0.995 0.983 0.924
2gk1 492 0.213 0.999 1.000 0.999
1o7a 486 2.411 0.952 0.913 0.802

Table TODO: </figtable>

iTasser


Modeller


3D-Jigsaw

References

<references/>

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