Difference between revisions of "Rs1800430"

From Bioinformatikpedia
(SNAP Prediction)
(Secondary Structure Mutation Analysis)
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=== Secondary Structure Mutation Analysis ===
 
=== Secondary Structure Mutation Analysis ===
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As a next step we compared the different results of the secondary structure prediction tools JPred and PsiPred. Afterwards we can examine in which secondary structure element and where therein the mutation takes place. This can give an overview of how drastical the mutation can be.
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In this case the tools disagree. JPred predict at the position of the mutation a coil and PsiPred predicted there a alpha-helix.
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For JPred a mutation at this position would not destroy or split a secondary structure element. It will probably only changes the coil between two secondary structure elements, but this can sometimes also cause a change of the the following secondary structure. We think that a drastical change of the protein structure and its function is unlikly for the JPred prediction.
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For PsiPred a mutation at the beginning of the alpha helix could inhibit the formation if this alpha helix. Therefore, we think that a this mutation would probably cause a extreme change in the protein structure and function.
   
 
JPred:
 
JPred:

Revision as of 12:36, 26 June 2011

General Information

SNP-id rs1800430
Codon 399
Mutation Codon Asn -> Asp
Mutation Triplet AAC -> GAC

Pysicochemical Properities

First of all, we explored the amino acid properties and compared them for the original and the mutated amino acid. Therefore we created the possible effect that the mutation could have on the protein.

Asn Asp consequences
polar, small, hydrophilic, negatively charged polar, small, hydrophilic, negatively charged Both amino acids have the same properities and therefore we suggest that an exchange of these two amino acids do not destroy the protein structure and function

Visualisation of the Mutation

In the next step, we created the visualization of the muation with PyMol. Therefore we created a picture for the original amino acid, for the new mutated amino acid and finally for both together in one picture whereas the mutation is white colored. The following pictures display that the mutated amino acid Aspartic acid looks very different to Asparagine. They both agree in the first part of the rest but then go complety in opposite directions. Otherwise both rests fork at the end. All in all, the different directions prevail and will therefore probably cause big structural changes which will cause effects on the protein function.

picture original aa picture mutated aa combined picture
Amino acid Asparagine
Amino acid Aspartic acid
Picture which visualize the mutation

Subsitution Matrices Values

Afterwards, we looked at the values of the substitution matrices PAM1, PAM250 and BLOSSUM62. Therefore we looked detailed at the three values: the value for accoding amino acid substitution, the most frequent value for the substitution of the examined amino acid and the rarest substitution.

In this case, the substitution of Asparagine to Aspartic acid has very high values that agree with the most frequent value for all three substitution matrices. Therefore, according to all matrices a mutation at this position will probably not cause structural changes which can affect functional changes.

PAM 1 Pam 250 BLOSOUM 62
value aa most frequent substitution rarest substitution value aa most frequent substitution rarest substitution value aa most frequent substitution rarest substitution
36 36 (Asp) 0 (Cys, Met) 7 7 (Asp) 2 (Cys, Leu, Phe, Trp) 1 1 (Asp, His, Ser) -4 (Trp)

PSSM analysis

self-information expected self-information
Asn 0 5
Asp 0 4

Conservation Analysis with Multiple Alignments

As a next step we created a multiple alignment which contains the HEXA sequence and 9 other mammalian homologous sequences from uniprot. Afterwards we looked at the position of the different mutations and looked at the conservation level on this position. The regarded mutation is presented by the first colored column. Here we can see, that almost all other mammalians have another amino acid or a gap on this position. Therefore, the mutation on this position is not highly conserved and a mutation there will cause probably no huge structural and functional changes for the protein.

Mutation in the multiple alignment

Secondary Structure Mutation Analysis

As a next step we compared the different results of the secondary structure prediction tools JPred and PsiPred. Afterwards we can examine in which secondary structure element and where therein the mutation takes place. This can give an overview of how drastical the mutation can be. In this case the tools disagree. JPred predict at the position of the mutation a coil and PsiPred predicted there a alpha-helix. For JPred a mutation at this position would not destroy or split a secondary structure element. It will probably only changes the coil between two secondary structure elements, but this can sometimes also cause a change of the the following secondary structure. We think that a drastical change of the protein structure and its function is unlikly for the JPred prediction. For PsiPred a mutation at the beginning of the alpha helix could inhibit the formation if this alpha helix. Therefore, we think that a this mutation would probably cause a extreme change in the protein structure and function.

JPred:
...CCCCCCCEEEEEECCCCCCCCHHHHHHHHHCCCCEEECCCCCCCCCCCCCCCCCC...
PsiPred:
...CCCCCCCCEEEEECCCCCCCHHHHHHHHHHCCCEEEECCCCCCCCCCCCCCCCCC...

Comparison with the real structure:

Mutation at position 399
Mutation at position 399 - detailed view

SNAP Prediction

Next, we looked at the result of the SNAP prediction. For this prediction we took the amino acid of the certain position and checked every possible amino acid mutation. Afterwards we extract the result for Aspartic acid which is the real mutation in this case. SNAP has a result that the exhange from Asparagine to Aspartic acid at this position is neutral with an average accuracy of 60%. This means that this certain mutation on this position cause likely no structural and functional changes of the protein.

Substitution Prediction Reliability Index Expected Accuracy
D Neutral 1 60%

A detailed list of all possible substitutions can be found [here]


SIFT Prediction

SIFT Matrix:
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.

Sift legend.png
399 sift.png.png

SIFT Table
Threshold for intolerance is 0.05.
Amino acid color code: nonpolar, uncharged polar, basic, acidic.
Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.



Predict Not ToleratedPositionSeq RepPredict Tolerated
wyfcm399N0.72iHvlgPtRDEQASKN




PolyPhen2 Prediction

HumDiv prediction
HumVar prediction