Short Introduction
This week's task builds on the data gathered last week. We blindly choose 5 disease causing and 5 harmless SNPs and will try to predict their effect from the sequence change alone. You may find a detailed task description at the usual place and consult our task journal.
Our dataset
we propose the following dataset:
- GLU76GLY
- SER87ARG
- GLN172HIS
- ARG158GLN
- ARG243GLN
- LEU255SER
- MET276VAL
- ALA322GLY
- GLY337VAL
- ARG408TRP
You could check them, if you like.. I put them together 5 minutes ago and already forgot, which are which. ;-)
Investigated SNPS
GLU76GLY
As this mutation results in a change from Glutamic acid to Glycine which have some differences in structure as can bee seen in <xr id="fig:mutationGLUGLY"/> we expect this change to be of rather minor effect. Of course Glutamic acid is charged under biological conditions and Glycine is not, but Glycine is kind of a universal substitution, because it is neither hydrophobic nor hydrophilic. Additionally, as it is the smallest amino acid, it can not produce any sterical problems. Of course it might be that the Glycine can not stabilize any structure, which should be present at this residue, but as we do not have any structural data for this point we only can rely on the physiochemical properties, for which we would say, that these changes are not drastic enough to cause the disease.
- Keychanges: [From negativly charged, polar, strongly hydrophilic, medium sized to neutral, non-polar, non-hydrophilic, small]
<figure id="fig:mutationGLUGLY">
Aminoacids in the first mutation
</figure>
2D structure projection of Glutamicacid with the pK-values for each group. For a better referability the c-atoms are labeled according to the common nomenclature
2D structure projection of Glycinewith the pK-values for each group. For a better referability the c-atoms are labeled according to the common nomenclature
SER87ARG
- Keychanges [From neutral, polar, slightly hydrophilic to pos. charged, polar, strongly hydrophilic]
ARG158GLN
From pos. charged, polar, strongly hydrophilic to neutral, polar, strongly hydrophilic.
Close-up of the mutated glutamine at residue 158 in PheOH. The best fitting rotamer was chosen to minimize severe or smaller collisions (red to green discs) with neighbouring residues. This rotamer appears in 1.7% of mutations according to the PyMol rotamer database.
Mutated glutamine at residue 158 in PheOH. The residue is located in a helix region and is statistically less likely in this type of structure than the original arginine.
GLN172HIS
From neutral, polar, strongly hydrophilic to neutral, polar, strongly hydrophilic, ring-structure
Close-up of the mutated histidine at residue 172 in PheOH. The best fitting rotamer was chosen to minimize severe or smaller collisions (red to green discs) with neighbouring residues. This rotamer appears in 18.9% of mutations according to the PyMol rotamer database.
Mutated histidine at residue 172 in PheOH. The residue is located in a coil region.
ARG243GLN
From pos. charged, polar, strongly hydrophilic to neutral, polar, strongly hydrophilic.
Close-up of the mutated histidine at residue 243 in PheOH. The best fitting rotamer was chosen to minimize severe or smaller collisions (red to green discs) with neighbouring residues. This rotamer appears in 17.3% of mutations according to the PyMol rotamer database.
Mutated glutamine at residue 243 in PheOH. The residue is located in a sheet region.
LEU255SER
From neutral, non polar, strongly hydrophobic to neutral, polar, slightly hydrophilic.
Close-up of the mutated serine at residue 255 in PheOH. The best fitting rotamer was chosen to minimize severe or smaller collisions (red to green discs) with neighbouring residues. This rotamer appears in 42.9% of mutations according to the PyMol rotamer database.
Mutated serine at residue 255 in PheOH. The residue is located in a helix region.
MET276VAL
From neutral, non-polar, hydrophobic to neutral, non-polar, strongly hydrophobic.
Close-up of the mutated XXXX at residue 276 in PheOH. The best fitting rotamer was chosen to minimize severe or smaller collisions (red to green discs) with neighbouring residues. This rotamer appears in XXX% of mutations according to the PyMol rotamer database.
Mutated XXX at residue 276 in PheOH. The residue is located in a XXX region.
ALA322GLY
From neutral, non-polar, hydrophobic, small to neutral, non-polar, slightly hydrophilic, small.
Close-up of the mutated XXXX at residue 322 in PheOH. The best fitting rotamer was chosen to minimize severe or smaller collisions (red to green discs) with neighbouring residues. This rotamer appears in XXX% of mutations according to the PyMol rotamer database.
Mutated XXX at residue 322 in PheOH. The residue is located in a XXX region.
GLY337VAL
From neutral, non-polar, slightly hydrophilic, small to neutral, non-polar, strongly hydrophobic, medium sized.
Close-up of the mutated XXXX at residue 337 in PheOH. The best fitting rotamer was chosen to minimize severe or smaller collisions (red to green discs) with neighbouring residues. This rotamer appears in XXX% of mutations according to the PyMol rotamer database.
Mutated XXX at residue 337 in PheOH. The residue is located in a XXX region.
ARG408TRP
From pos. charged, polar, strongly hydrophilic, medium sized to neutral, non-polar, slightly hydrophilic, large.
Close-up of the mutated XXXX at residue 408 in PheOH. The best fitting rotamer was chosen to minimize severe or smaller collisions (red to green discs) with neighbouring residues. This rotamer appears in XXX% of mutations according to the PyMol rotamer database.
Mutated XXX at residue 408 in PheOH. The residue is located in a XXX region.
References
A helix propensity scale based on experimental studies of peptides and proteins.
