Difference between revisions of "Fabry:Structure-based mutation analysis"
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− | ==foldX== |
+ | === foldX === |
+ | <div style="float:left; border:thin solid lightgrey; margin: 0px 0px 0px 0px;"> |
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+ | <figtable id="tab:energyStart"> |
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+ | <caption>ADD CAPTION HERE</caption> |
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+ | {| class="wikitable sortable" style="border-collapse: collapse; border-spacing: 0; border-width: 1px; border-style: solid; padding-left:5px; padding-right:5px; border-color: #000; padding: 0" |
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+ | ! style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Type |
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+ | ! style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Energy |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| BackHbond |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| -528.41 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| SideHbond |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| -149.96 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Energy_VdW |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| -1013.85 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Electro |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| -25.51 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Energy_SolvP |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 1310.89 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Energy_SolvH |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| -1318.53 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Energy_vdwclash |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 99.21 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| energy_torsion |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 26.73 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| backbone_vdwclash |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 478.11 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Entropy_sidec |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 482.20 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Entropy_mainc |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 1219.31 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| water bonds |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| -29.53 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| helix dipole |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| -12.51 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| loop_entropy |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 0.00 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| cis_bond |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 4.50 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| disulfide |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| -29.93 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| kn electrostatic |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| -0.98 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| partial covalent interactions |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 0.00 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Energy_Ionisation |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 1.20 |
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+ | |- |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Entropy Complex |
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+ | | style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 0.00 |
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+ | |- |
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+ | ! style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0;"| Total |
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+ | ! style="border-style: solid; padding-left:5px; padding-right:5px; border-width: 0 1px 1px 0; text-align:right"| 34.82 |
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+ | |- |
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+ | |} |
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+ | </figtable> |
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+ | </div> |
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+ | <br style="clear:both"> |
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+ | === Minimise === |
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− | ==Minimise== |
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+ | === Gromacs === |
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− | |||
− | == Gromacs == |
Revision as of 10:52, 21 June 2012
Fabry Disease » Structure-based mutation analysis
The following analyses were performed on the basis of the α-Galactosidase A sequence. Please consult the journal for the commands used to generate the results.
Contents
Preparation
<figtable id="tab:Prep">
All available PDB structures assigned to the Uniprot entry P06280 along with the according Resolution,
Coverage and R-factor. The R-factor was obtained from the PDBsum page. The chosen structure 3S5Y is highlighted.
Entry | Method | Resolution (Å) | Chain | Positions (up to 429) | R-factor | R-free | pH | PDBsum | PDB |
---|---|---|---|---|---|---|---|---|---|
1R46 | X-ray | 3.25 | A/B | 32-422 | 0.262 | 0.301 | 8.0 | [»] | [»] |
1R47 | X-ray | 3.45 | A/B | 32-422 | 0.285 | 0.321 | 8.0 | [»] | [»] |
3GXN | X-ray | 3.01 | A/B | 32-421 | 0.239 | 0.301 | 4.5 | [»] | [»] |
3GXP | X-ray | 2.20 | A/B | 32-422 | 0.204 | 0.265 | 4.5 | [»] | [»] |
3GXT | X-ray | 2.70 | A/B | 32-422 | 0.245 | 0.306 | 4.5 | [»] | [»] |
3HG2 | X-ray | 2.30 | A/B | 32-422 | 0.178 | 0.202 | 4.6 | [»] | [»] |
3HG3 | X-ray | 1.90 | A/B | 32-426 | 0.167 | 0.197 | 6.5 | [»] | [»] |
3HG4 | X-ray | 2.30 | A/B | 32-423 | 0.166 | 0.221 | 4.6 | [»] | [»] |
3HG5 | X-ray | 2.30 | A/B | 32-422 | 0.192 | 0.227 | 4.6 | [»] | [»] |
3LX9 | X-ray | 2.04 | A/B | 32-422 | 0.178 | 0.218 | 6.5 | [»] | [»] |
3LXA | X-ray | 3.04 | A/B | 32-426 | 0.216 | 0.244 | 6.5 | [»] | [»] |
3LXB | X-ray | 2.85 | A/B | 32-427 | 0.227 | 0.264 | 6.5 | [»] | [»] |
3LXC | X-ray | 2.35 | A/B | 32-422 | 0.186 | 0.237 | 6.5 | [»] | [»] |
3S5Y | X-ray | 2.10 | A/B | 32-422 | 0.195 | 0.230 | 5.1 | [»] | [»] |
3S5Z | X-ray | 2.00 | A/B | 32-421 | 0.211 | 0.234 | 5.1 | [»] | [»] |
3TV8 | X-ray | 2.64 | A/B | 32-422 | 0.203 | 0.239 | 4.6 | [»] | [»] |
</figtable>
We did not choose the structure 3HG3, although it has the best resolution (1.90 Å) and the second best R-factor (see <xr id="tab:Prep"/>), which is a measure of the agreement between the crystallographic model and the experimental X-ray diffraction data <ref>R-factor (crystallography) (May 17, 2012) http://en.wikipedia.org/wiki/R-factor_%28crystallography%29, June 20, 2012</ref>, since it has an Alanin at position 170 (part of the active site) instead of an Aspartic acid. After excluding those structures, that had deviations in the sequence, we had to choose between ten sequences (1R46, 1R47, 3GXN, 3GXP, 3GXT, 3HG2, 3HG4, 3HG5, 3S5Y, 3S5Z) and decided to use 3S5Y. This structure has the advantage of a good pH, very good coverage and still reasonable resolution and R-factor.
Vizualisation
Create mutation
SCWRL
Comparison energies
foldX
<figtable id="tab:energyStart"> ADD CAPTION HERE
Type | Energy |
---|---|
BackHbond | -528.41 |
SideHbond | -149.96 |
Energy_VdW | -1013.85 |
Electro | -25.51 |
Energy_SolvP | 1310.89 |
Energy_SolvH | -1318.53 |
Energy_vdwclash | 99.21 |
energy_torsion | 26.73 |
backbone_vdwclash | 478.11 |
Entropy_sidec | 482.20 |
Entropy_mainc | 1219.31 |
water bonds | -29.53 |
helix dipole | -12.51 |
loop_entropy | 0.00 |
cis_bond | 4.50 |
disulfide | -29.93 |
kn electrostatic | -0.98 |
partial covalent interactions | 0.00 |
Energy_Ionisation | 1.20 |
Entropy Complex | 0.00 |
Total | 34.82 |
</figtable>