Gaucher Disease: Task 03 - Sequence-based predictions

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Revision as of 18:22, 26 May 2013 by Gerkej (talk | contribs) (Transmembrane Helices)

Secondary Structure

TODO: What features are predicted? Discuss the results for your protein and the example proteins. Using the predictions, what could you learn about your protein and the example proteins? Compare to the available knowledge in UniProt, PDB, DisProt, OPM, PDBTM, Pfam...

Disorder

Transmembrane Helices

Four Proteins, including the Gaucher's disease causing Protein, where analysed under reference by transmembrane helices. The used prediction tools differ in their analysing features. While Polyphobius only differs between residues being part of a transmembrane helix or being inside/outside of the cytoplama, Memsat-SVM also predicts re-entrant helices and pore-linig helices. Due to the fact that pore-lining helices are also transmembrane helices, this kind of helices is detected of both prediction tools. In case of re-entrant helices both programms differ. Polyphobius takes this helix as a membrane helix, but Memsat-SVM predicts a re-entrant helix outside the membrane. Therefore the number of the transmembrane hlices, predicted by the tools, differ from each other. In this case also the c-terminal may be predicted in a different area because of an additional helix.

Position of Q9YDF8 in the membrane, predicted with Memsat-SVM


Comparison of TMH for Q9YDF8
Prediction Assignment
Memsat SVM Polyphobius OPM PDMTM
# of TMH 6 7
TMH Topology 43-59
72-90
101-118
128-143
163-184

221-245
42-60
68-88
108-129
137-157
163-184
196-213
224-244
N-terminal cytoplasmic extracellular
C-terminal cytoplasmic cytoplasmic
Signal peptide - -
Re-entrant Helix 188-217 -
Pore-linig Helix 1 -
Graphical position
Position of Q9YDF8 in the membrane, predicted with Memsat-SVM

Signal Peptides

GO Terms

Discussion

Other available methods

Prediction of Tool Information
secondary structure GOR http://gor.bb.iastate.edu/
disorder DISOPRED2 http://bioinf.cs.ucl.ac.uk/psipred/
transmembrane helices MEMSAT3 http://bioinf.cs.ucl.ac.uk/psipred/
TMHMM http://www.cbs.dtu.dk/services/TMHMM/
signal peptides
GO terms

What else can/is be predicted from protein sequence alone

  • Fold recognition (profile based pGenTHREADER and rapid GenTHREADER)
  • Fold domain recognition (pDomTHREADER)
  • Protein domain prediction (DomPred)
  • Homology modelling (BioSerf v2.0)
  • Function prediction (eukaryotic function: FFPred v2.0)
  • Prediction of TM topology and helix packing (SVM-based MEMPACK)

http://bioinf.cs.ucl.ac.uk/psipred/

Which predictions can be improved considerably by structure-based approaches