Difference between revisions of "Rs121907979"

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(Secondary structure mutation analysis)
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=== Secondary structure mutation analysis ===
=== Secondary Structure Mutation Analysis ===

Revision as of 17:55, 23 June 2011

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.

Leu Arg consequences
aliphatic, hydrophobic, neutral positive charged, polar, hydrophilic Leucine is smaller and without a positive charge. Therefore, Arg is too big for the position of Leu, therefore, the change of Leu with Arg has to cause changes in the 3D structure of the protein. Furthermore, Leu is a hydrophobic amino acid, whereas Arg is hydrophilic. This is the complete contrary and therefore we suggest, that the protein will not function any longer.

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 Arginine has a longer chain than Leucine. Contrary Leucine comes to a fork at the end of its rest. This shows that the amino acids have some structural differences that are not drastical, but can be essential.

picture original aa picture mutated aa combined picture
Amino acid Leucine
Amino acid Arginine
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 Leucine to Arginine has very low values that are near the values for the rarest subsitution for PAM1 and PAM250. Furthermore, the value for the most frequent substitution differs also a lot from the value for this certain mutation for both PAMs. Contrary for BLOSUM62 the value for the amino acid subsitution Leucine to Arginine is average. This means the most frequent subsitution value is as far as the rarerest subsitution from the the underlying value. The difference between the two PAMs and BLOSUM62 can be ascribed to the different preparations of these two kind of substitutions matrices. The PAM-matrices is an evolutionary model whereas BLOSUM is based on protein famalies. Therefore probably this mutation is evolutionary not that unlikely whereas within a protein family it is unusual.

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
1 22 (Ile) 0 (Asp, Cys) 4 20 (Met) 2 (Cys) -2 0 (Phe) -4 (Asp, Gly)

Conservation analysis with multiple alignments

Mutation in the multiple alignment

Secondary Structure Mutation Analysis


Comparison with the real structure:

Mutation at position 39
Mutation at position 39 - detailed view

SNAP Prediction

Substitution Prediction Reliability Index Expected Accuracy
R Non-neutral 5 87%

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
39 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

Polyphen2 Prediction

HumDiv prediction
HumVar prediction