Difference between revisions of "ASPA Structure Based Mutation Analysis"
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| − | + | ==FoldX== |
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| + | |||
| + | Running foldx on our protein and its mutated versions returned the following results: |
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| − | ===Minimise=== |
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| + | |||
| + | |||
| + | ===Gromacs=== |
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| + | |||
| + | The script fetchPDB used to download the PDB file first pulls the gzipped version of the PDB file from the PDB website, then unpacks it. |
||
| + | |||
| + | We cleaned the PDB file using repairPDB with the options <tt>-nosol</tt> and <tt>-noh</tt> to extract just the protein. Other options available include <tt>-seq</tt>, which extracts the protein sequence and return it as a string and <tt>-cleansol</tt>, which cleans up the solvent for use with Gromacs. |
||
| + | |||
| + | We afterwards extracted chain A; since both chains show little in the way of diffences, we decided to use A. |
||
| + | |||
| + | Then we generated mutated PDBs using SCWRL; we had to extract the sequence of the protein from the PDB file beforehand using repairPDB with the option <tt>-seq</tt> and edit it to be lowercase with just the mutated position in uppercase. |
||
| + | |||
| + | We measured the run time for different values for <tt>nsteps</tt> and plotted the results in a graph, with <tt>nsteps</tt> on the x axis and the time in seconds on the y axis. |
||
| + | |||
| + | [[File:ASPA Timegraph.png]] |
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| + | |||
| + | |||
| + | |||
| + | ==PyMol Pictures== |
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| + | |||
| + | The following pictures were created using PyMOL to illustrate the effects of the mutations generated by SCWRL: |
||
| + | |||
| + | <table> |
||
| + | <tr><td> </td><td align=center><b>Wildtype</b></td><td align=center><b>Mutation</b></td></tr> |
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| + | <tr><td><b>RS104894553</b></td><td>[[File:Wt rs104894553.png|500px]]</td><td>[[File:Mut rs104894553.png|500px]]</td></tr> |
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| + | <tr><td><b>CM940124</b></td><td>[[File:Wt cm940124.png|500px]]</td><td>[[File:Mut cm940124.png|500px]]</td></tr> |
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| + | <tr><td><b>CM063847</b></td><td>[[File:Wt cm063847.png|500px]]</td><td>[[File:Mut cm063847.png|500px]]</td></tr> |
||
| + | <tr><td><b>RS80099330</b></td><td>[[File:Wt rs80099330.png|500px]]</td><td>[[File:Mut rs80099330.png|500px]]</td></tr> |
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| + | <tr><td><b>CM990193</b></td><td>[[File:Wt cm990193.png|500px]]</td><td>[[File:Mut cm990193.png|500px]]</td></tr> |
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| + | <tr><td><b>RS104894548</b></td><td>[[File:Wt rs104894548.png|500px]]</td><td>[[File:Mut rs104894548.png|500px]]</td></tr> |
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| + | <tr><td><b>CM990195</b></td><td>[[File:Wt cm990195.png|500px]]</td><td>[[File:Mut cm990195.png|500px]]</td></tr> |
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| + | <tr><td><b>CM055097</b></td><td>[[File:Wt cm055097.png|500px]]</td><td>[[File:Mut cm055097.png|500px]]</td></tr> |
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| + | <tr><td><b>RS104894551</b></td><td>[[File:Wt rs104894551.png|500px]]</td><td>[[File:Mut rs104894551.png|500px]]</td></tr> |
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| + | <tr><td><b>CM994594</b></td><td>[[File:Wt cm994594.png|500px]]</td><td>[[File:Mut cm994594.png|500px]]</td></tr> |
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| + | </table> |
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| + | |||
| + | |||
| + | |||
| + | ==Results of the Minimization== |
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| + | |||
| + | Minimise returned the following energies: |
||
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| + | The following graphs illustrate the results of the minimization step. |
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| − | |||
| − | |||
| − | |||
| − | ===Gromacs=== |
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| − | |||
| − | [[File:ASPA Timegraph.png]] |
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| − | |||
| − | |||
| − | ===Pictures=== |
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| − | <table> |
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| − | <tr><td> </td><td align=center><b>Wildtype</b></td><td align=center><b>Mutation</b></td></tr> |
||
| − | <tr><td><b>RS104894553</b></td><td>[[File:Wt rs104894553.png|500px]]</td><td>[[File:Mut rs104894553.png|500px]]</td></tr> |
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| − | <tr><td><b>CM940124</b></td><td>[[File:Wt cm940124.png|500px]]</td><td>[[File:Mut cm940124.png|500px]]</td></tr> |
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| − | <tr><td><b>CM063847</b></td><td>[[File:Wt cm063847.png|500px]]</td><td>[[File:Mut cm063847.png|500px]]</td></tr> |
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| − | <tr><td><b>RS80099330</b></td><td>[[File:Wt rs80099330.png|500px]]</td><td>[[File:Mut rs80099330.png|500px]]</td></tr> |
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| − | <tr><td><b>CM990193</b></td><td>[[File:Wt cm990193.png|500px]]</td><td>[[File:Mut cm990193.png|500px]]</td></tr> |
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| − | <tr><td><b>RS104894548</b></td><td>[[File:Wt rs104894548.png|500px]]</td><td>[[File:Mut rs104894548.png|500px]]</td></tr> |
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| − | <tr><td><b>CM990195</b></td><td>[[File:Wt cm990195.png|500px]]</td><td>[[File:Mut cm990195.png|500px]]</td></tr> |
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| − | <tr><td><b>CM055097</b></td><td>[[File:Wt cm055097.png|500px]]</td><td>[[File:Mut cm055097.png|500px]]</td></tr> |
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| − | <tr><td><b>RS104894551</b></td><td>[[File:Wt rs104894551.png|500px]]</td><td>[[File:Mut rs104894551.png|500px]]</td></tr> |
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| − | <tr><td><b>CM994594</b></td><td>[[File:Wt cm994594.png|500px]]</td><td>[[File:Mut cm994594.png|500px]]</td></tr> |
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| − | </table> |
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| − | |||
| − | |||
| − | |||
| − | |||
<b>cm055097</b><table><tr><td>Average</td><td>Err.Est.</td><td>RMSD</td><td>Tot-Drift</td><td></td></tr> |
<b>cm055097</b><table><tr><td>Average</td><td>Err.Est.</td><td>RMSD</td><td>Tot-Drift</td><td></td></tr> |
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Latest revision as of 23:05, 31 August 2011
FoldX
Running foldx on our protein and its mutated versions returned the following results:
| Mutation | BackHbond | SideHbond | Energy_VdW | Electro | SolvP | SolvH | vdwclash | torsion | bb_vdwclash | Entropy_sidec | Entropy_mainc | water bonds | helix dipole | loop_entropy | cis_bond | disulfide | kn electrostatic | partial covalent interactions | Ionisation | Entropy Complex | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| WT | -351.60 | -113.32 | -753.77 | -34.77 | 991.74 | -1003.86 | 94.80 | 42.16 | 375.34 | 372.13 | 941.00 | -1.73 | -1.78 | 0.00 | 9.05 | 0.00 | -0.94 | -26.09 | 2.96 | 0.00 | 165.97 |
| CM055097 | -355.76 | -113.21 | -759.56 | -33.94 | 986.09 | -1010.92 | 170.97 | 80.70 | 377.29 | 374.36 | 942.29 | 0.00 | -1.21 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 3.65 | 0.00 | 291.86 |
| CM063847 | -355.74 | -112.37 | -759.94 | -34.09 | 985.12 | -1012.35 | 178.46 | 80.88 | 377.32 | 374.49 | 942.56 | 0.00 | -1.44 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 3.68 | 0.00 | 297.66 |
| CM940124 | -355.67 | -113.51 | -760.79 | -33.98 | 989.54 | -1012.11 | 185.56 | 80.68 | 377.55 | 375.73 | 942.35 | 0.00 | -1.76 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 3.64 | 0.00 | 308.08 |
| CM990193 | -355.77 | -113.23 | -760.51 | -33.74 | 987.84 | -1011.65 | 194.71 | 80.60 | 377.51 | 374.59 | 944.00 | 0.00 | -1.44 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 3.79 | 0.00 | 317.61 |
| CM990195 | -355.82 | -113.22 | -759.67 | -34.61 | 989.16 | -1009.25 | 179.53 | 80.75 | 377.29 | 374.77 | 942.43 | 0.00 | -1.36 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 3.64 | 0.00 | 304.76 |
| CM994594 | -355.60 | -113.20 | -756.93 | -33.66 | 982.92 | -1007.28 | 169.81 | 80.49 | 376.73 | 373.69 | 941.91 | 0.00 | -1.44 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 3.64 | 0.00 | 292.75 |
| RS104894548 | -355.81 | -113.21 | -760.68 | -33.70 | 989.00 | -1011.59 | 187.60 | 80.73 | 377.34 | 375.06 | 942.60 | 0.00 | -1.39 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 3.64 | 0.00 | 310.63 |
| RS104894551 | -355.68 | -113.48 | -757.12 | -31.38 | 979.51 | -1008.38 | 168.90 | 80.33 | 376.85 | 372.68 | 942.57 | 0.00 | -1.45 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 3.11 | 0.00 | 288.02 |
| RS104894553 | -355.73 | -113.24 | -759.08 | -35.12 | 985.71 | -1010.41 | 173.40 | 80.55 | 377.28 | 374.26 | 942.65 | 0.00 | -1.41 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 4.03 | 0.00 | 294.00 |
| RS80099330 | -355.61 | -113.21 | -758.06 | -33.77 | 984.24 | -1008.91 | 170.10 | 80.58 | 377.03 | 373.24 | 942.10 | 0.00 | -1.44 | 0.00 | 9.03 | 0.00 | -0.63 | 0.00 | 3.64 | 0.00 | 291.29 |
Gromacs
The script fetchPDB used to download the PDB file first pulls the gzipped version of the PDB file from the PDB website, then unpacks it.
We cleaned the PDB file using repairPDB with the options -nosol and -noh to extract just the protein. Other options available include -seq, which extracts the protein sequence and return it as a string and -cleansol, which cleans up the solvent for use with Gromacs.
We afterwards extracted chain A; since both chains show little in the way of diffences, we decided to use A.
Then we generated mutated PDBs using SCWRL; we had to extract the sequence of the protein from the PDB file beforehand using repairPDB with the option -seq and edit it to be lowercase with just the mutated position in uppercase.
We measured the run time for different values for nsteps and plotted the results in a graph, with nsteps on the x axis and the time in seconds on the y axis.
PyMol Pictures
The following pictures were created using PyMOL to illustrate the effects of the mutations generated by SCWRL:
| Wildtype | Mutation | |
| RS104894553 |  |  |
| CM940124 |  |  |
| CM063847 |  |  |
| RS80099330 |  |  |
| CM990193 |  |  |
| RS104894548 |  |  |
| CM990195 |  |  |
| CM055097 |  |  |
| RS104894551 |  |  |
| CM994594 |  |  |
Results of the Minimization
Minimise returned the following energies:
| Mutation | WT | cm055097 | cm063847 | cm940124 | cm990193 | cm990195 | cm994594 | rs104894548 | rs104894551 | rs104894553 | rs80099330 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Energy | -14776.478983 | -14054.020681 | -12533.719784 | -11003.916326 | -12670.140717 | -11757.261266 | -14164.353463 | -8677.102143 | -14220.689449 | -14035.011150 | -14141.901598 |
The following graphs illustrate the results of the minimization step.
cm055097
Mut 2O53 cm055097 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
cm055097
Mut 2O53 cm055097 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
cm055097
Mut 2O53 cm063847 onlyprot A gromacs angle.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
cm063847
Mut 2O53 cm063847 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
cm063847
Mut 2O53 cm063847 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
cm063847
Mut 2O53 cm940124 onlyprot A gromacs angle.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
cm940124
Mut 2O53 cm940124 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
cm940124
Mut 2O53 cm940124 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
cm940124
Mut 2O53 cm990193 onlyprot A gromacs angle.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
cm990193
Mut 2O53 cm990193 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
cm990193
Mut 2O53 cm990193 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
cm990193
Mut 2O53 cm990195 onlyprot A gromacs angle.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
cm990195
Mut 2O53 cm990195 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
cm990195
Mut 2O53 cm990195 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
cm990195
Mut 2O53 cm994594 onlyprot A gromacs angle.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
cm994594
Mut 2O53 cm994594 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
cm994594
Mut 2O53 cm994594 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
cm994594
Mut 2O53 rs104894548 onlyprot A gromacs angle.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
rs104894548
Mut 2O53 rs104894548 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
rs104894548
Mut 2O53 rs104894548 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
rs104894548
Mut 2O53 rs104894551 onlyprot A gromacs angle.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
rs104894551
Mut 2O53 rs104894551 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
rs104894551
Mut 2O53 rs104894551 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
rs104894551
Mut 2O53 rs104894553 onlyprot A gromacs angle.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
rs104894553
Mut 2O53 rs104894553 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
rs104894553
Mut 2O53 rs104894553 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
rs104894553
Mut 2O53 rs80099330 onlyprot A gromacs angle.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
rs80099330
Mut 2O53 rs80099330 onlyprot A gromacs bond.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| angle | avg | errest | rmsd | totdrift |  |
rs80099330
Mut 2O53 rs80099330 onlyprot A gromacs potential.png
| Average | Err.Est. | RMSD | Tot-Drift | ||
| bond | avg | errest | rmsd | totdrift |  |
rs80099330
| Average | Err.Est. | RMSD | Tot-Drift | ||
| potential | avg | errest | rmsd | totdrift |  |
