Difference between revisions of "Structure-based mutation analysis ARSA"
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===== Mutation 1 ===== |
===== Mutation 1 ===== |
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| + | We also ran SCWRL on the wild type (wt) structure in order to make it comparable to energy predictions by other programs. The minimal energy of the graph for the wt is 415.134. |
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{| border="1" style="text-align:left; border-spacing:0;" |
{| border="1" style="text-align:left; border-spacing:0;" |
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| ''' both (without H-bonds) ''' |
| ''' both (without H-bonds) ''' |
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| ''' Minimal energy ''' |
| ''' Minimal energy ''' |
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| + | | ''' Energy(mutant)/Energy(wt) |
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|[[Image:arsa_both29.png|200px]] |
|[[Image:arsa_both29.png|200px]] |
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|419.996 |
|419.996 |
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| + | |1.011712 |
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| 2 |
| 2 |
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|[[Image:arsa_both136.png|200px]] |
|[[Image:arsa_both136.png|200px]] |
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|415.133 |
|415.133 |
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| + | |0.9999976 |
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|[[Image:arsa_both153.png|200px]] |
|[[Image:arsa_both153.png|200px]] |
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|420.494 |
|420.494 |
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| + | |1.012911 |
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|[[Image:arsa_both193.png|200px]] |
|[[Image:arsa_both193.png|200px]] |
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|416.252 |
|416.252 |
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| + | |1.002693 |
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|[[Image:arsa_both274.png|200px]] |
|[[Image:arsa_both274.png|200px]] |
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|434.014 |
|434.014 |
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| + | |1.045479 |
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|[[Image:arsa_both356.png|200px]] |
|[[Image:arsa_both356.png|200px]] |
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|415.134 |
|415.134 |
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| + | |1 |
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| + | | |
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| 7 |
| 7 |
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|[[Image:arsa_both409.png|200px]] |
|[[Image:arsa_both409.png|200px]] |
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|414.481 |
|414.481 |
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| + | |0.998427 |
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| 8 |
| 8 |
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|[[Image:arsa_both440.png|200px]] |
|[[Image:arsa_both440.png|200px]] |
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|418.863 |
|418.863 |
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| + | |1.008983 |
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| 9 |
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|[[Image:arsa_both489.png|200px]] |
|[[Image:arsa_both489.png|200px]] |
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|415.136 |
|415.136 |
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| + | |1.000005 |
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| 10 |
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|[[Image:arsa_both496.png|200px]] |
|[[Image:arsa_both496.png|200px]] |
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|421.011 |
|421.011 |
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| + | |1.014157 |
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Revision as of 13:56, 30 June 2011
Preparation
Visualization with Pymol
The following image shows a pymol visualization of Arylsulfatase A, together with all known active and binding sites.
One can see, that the mutations are spread out through the protein. Some lie near functional sites, other are very distant from them. The table below shows again Pymol visualizations of all mutations, but each seperately. With this, we want to try to derive investigate the correlation of location of the mutation with respect to functional sites and its effect on the protein function.
| Nr. | mutation | position | Pymol image | Description | Effect on function |
| 1 | Asp-Asn | 29 | The mutation is located at the position of a metal-binding site. | harmful | |
| 2 | Pro - Ala | 136 | The mutation is located near the active site and a substrate binding site in sequence as well as in structure. | harmful | |
| 3 | Gln-His | 153 | The mutation is located near the active site and a substrate binding site in sequence as well as in structure. | harmful | |
| 4 | Trp-Cys | 193 | The mutation is at moderate distance to all important functional sites of the protein. | neutral | |
| 5 | Thr-Met | 274 | The mutation is located very distant from the active site and a substrate binding site in sequence as well as in structure. It is located within a beta sheet. |
harmful | |
| 6 | Phe -Val | 356 | The mutation is at moderate distance to all important functional sites of the protein. | neutral | |
| 7 | Thr-Ile | 409 | The mutation is not close to important functional sites. | harmful | |
| 8 | Asn-Ser | 440 | The mutation is very distant from all functional sites. | neutral | |
| 9 | Cys-Gly | 489 | The mutation is very distant from all functional sites. | harmful | |
| 10 | Arg-His | 496 | The mutation is very distant from all functional sites. | harmful |
Above visualizations indicate, that mutations near functional important sites of the protein are likely to cause a harmful effect. However, for distant mutations no trend can be observed.
SCRWL
First, we extracted the amino acid sequence from our pdb file and converted it to lower case.
repairPDB arsa_model.pdb -seq > arsa.model.seq
tr '[:upper:]' '[:lower:]' < arsa.model.seq > arsa.model.lower.seq
Next, we included the individual mutations as capital letters in seperate files and executed scwrl with the following command:
scwrl cmd
Mutation 1
We also ran SCWRL on the wild type (wt) structure in order to make it comparable to energy predictions by other programs. The minimal energy of the graph for the wt is 415.134.
| Nr. | mutation | position | Reference amino acid | mutated amino acid | both (without H-bonds) | Minimal energy | Energy(mutant)/Energy(wt) | |
| 1 | Asp-Asn | 29 | 
|
|
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419.996 | 1.011712 | |
| 2 | Pro - Ala | 136 | 
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|
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415.133 | 0.9999976 | |
| 3 | Gln-His | 153 | 
|
|
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420.494 | 1.012911 | |
| 4 | Trp-Cys | 193 | 
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|
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416.252 | 1.002693 | |
| 5 | Thr-Met | 274 | 
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|
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434.014 | 1.045479 | |
| 6 | Phe -Val | 356 | 
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415.134 | 1 | |
| 7 | Thr-Ile | 409 | 
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414.481 | 0.998427 | |
| 8 | Asn-Ser | 440 | 
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418.863 | 1.008983 | |
| 9 | Cys-Gly | 489 | 
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415.136 | 1.000005 | |
| 10 | Arg-His | 496 | 
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421.011 | 1.014157 |
