Normal mode analysis (Phenylketonuria)

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Summary

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Normal Mode Analysis

Lab journal
For the analysis, we used the pdb structure 1J8U from the task before (Task 9 - Structure-based mutation analysis).

WEBnm@

<figure id="webMode">

Normalized squared displacement per residue for mode 7 to 12. The x-axis represent the residue number in the sequence, whereby 0 is the first of the structure sequence, which is residue 103 in the FASTA-sequence of P00439. the y-axis shows the normalized squared displacement.

</figure>

Mode 7

<figure id="web_mode7">

Mode 7 captured of WEBnm@. The PAH structure (pdb 1j8u) is shown in transperent green, the ligands in red (H4B: C₉H₁₅N₅O₃) and orange (Fe₂). The blue doted lines represent the movement of the structure.

</figure>

This mode seems to have a high movement as the blue doted lines in <xr id="web_mode7"/> are relatively long. Furthermore they seem to open and close on all sites the same, which gives the imagine of a pump and not a twist. This also can be viewed in the first picture to the top left of <xr id="webMode"/>. Between residues 20 and 30 there is a high atomic displacement which also can be seen for residues 240 to 300.

Mode 8

<figure id="web_mode8">

Mode 8 captured of WEBnm@. The PAH structure (pdb 1j8u) is shown in transperent green, the ligands in red (H4B: C₉H₁₅N₅O₃) and orange (Fe₂). The blue doted lines represent the movement of the structure.

</figure>

Mode 8 of WEBnm@ show a few differences to mode 7 as there seems only be a atomic displacement at residues 20 to 50 (<xr id="webMode"/> top right). In <xr id="web_mode8"/> you can see that this is represented in the picture on the right site of the binding site. Maybe this helps the protein to bind or release a substrate.

Mode 9

<figure id="web_mode9">

Mode 9 captured of WEBnm@.The PAH structure (pdb 1j8u) is shown in transperent green, the ligands in red (H4B: C₉H₁₅N₅O₃) and orange (Fe₂). The blue doted lines represent the movement of the structure.

</figure>

Like in the mode before there is only a part of the protein which shows a high atomic displacement, which can be found at the residues 280 to 310 (<xr id="webMode"/>). ...

Mode 10

<figure id="web_mode10">

Mode 10 captured of WEBnm@. The PAH structure (pdb 1j8u) is shown in transperent green, the ligands in red (H4B: C₉H₁₅N₅O₃) and orange (Fe₂). The blue doted lines represent the movement of the structure.

</figure>

Mode 10 shows a high atomic displacement in some parts of the protein. Especially in the beginning before residue 50 and again after residue 280 (<xr id="webMode"/>). However, in <xr id="web_mode10"/> there seems to be not that high movements. ...

Mode 11

<figure id="web_mode11">

Mode 11 captured of WEBnm@. The PAH structure (pdb 1j8u) is shown in transperent green, the ligands in red (H4B: C₉H₁₅N₅O₃) and orange (Fe₂). The blue doted lines represent the movement of the structure.

</figure>

This mode seems to have some similarities with mode 10 before in the atomic displacement as there is a high atomic displacement in the beginning and in the end of the protein ((<xr id="webMode"/>, bottom left). However, looking at <xr id="web_mode11"/> some differences can be viewed like in the bottom left of the picture, where you can see that the movement has another direction.

Mode 12

<figure id="web_mode12">

Mode 12 captured of WEBnm@. The PAH structure (pdb 1j8u) is shown in transperent green, the ligands in red (H4B: C₉H₁₅N₅O₃) and orange (Fe₂). The blue doted lines represent the movement of the structure.

</figure>

The last mode provided by WEBnm@ here shows highest atomic displacement at residues 25 to 50 (<xr id="webMode"/>, bottom right). In <xr id="web_mode12"/> you can see ...

<figure id="correlation">

Correlation matrix of 1J8U for the residues 103 to 427 of the FASTA sequence. Red color stands for positive correlations and blue for negative.

</figure>

elNémo

ElNémo computes models for the given protein 1J8U. Thereby it calculates 100 lowest-frequency modes and provides a lot of information about the modes with different parameters and visualizations:

• PDB-files with the conformations of the modes
• animations of the modes of three different sites
• CA-vari (calculates distance fluctuations between all C-alpha atoms)
• R² residue mean square displacement of all C-alpha atoms
• Frequency and collectivity of the modes

<figtable id="frecol">

First five modes
Mode	Frequency	Collectivity
mode 7	1.00	0.5475
mode 8	1.02	0.4062
mode 9	1.36	0.2941
mode 10	1.43	0.0948
mode 11	1.60	0.3466

...

</figtable>

• B-factor analysis for the correlation between observed and normal-mode-derived atomi displacement parameters:

  Correlation = 0.534 for 307 C-alpha atoms

• RMSD: only if two structures are used

Theoretical every number of normal mode perturbed models can be generated. However, a high number would take a lot of time. On default five normal modes will be computed by elNémo and can be increased up to 25. Additionally more normal modes can be calculated after the run. The analyses of the five modes with lowest frequency normal modes are shown below. For the calculation of the models all atoms are used.

Mode 7

<figure id="mode7_gif">

Representation of the PAH (pdb 1J8U) movement calculated by elNémo.

</figure>

<figure id="mode7_matrix">

Matrix showing the maximal distance fluctuation of PAH (pdb 1J8U). If the distances decrease they are plotted in red, whereas increasing distances are shown in blue, but only if they are under the 10% strongest distance changes.

</figure>

Like mode 7 of WEBnm@ this mode of elNémo seems to have a pumping movement or "breathing" (<xr id="mode7_gif"/>). In principal the whole protein seems to be part of the fluctuation including the β-strand shown in red. The matrix in <xr id="mode7_matrix"/> also shows both increasing and decreasing distances spread over the whole protein.

Mode 8

<figure id="mode8_gif">

Representation of the PAH (pdb 1J8U) movement calculated by elNémo.

</figure> <figure id="mode8_matrix">

Matrix showing the maximal distance fluctuation of PAH (pdb 1J8U). If the distances decrease they are plotted in red, whereas increasing distances are shown in blue, but only if they are under the 10% strongest distance changes.

</figure>

In <xr id="mode8_gif"/> you can see that the protein opens and closes at the binding site, whereby it looks like an opening and closing mouth. So this mode shows a hinge-movement for our protein PAH. Additionally in the correlation matrix (<xr id="mode8_matrix"/>) only small parts of the protein seem to move at all and the distances hardly ever increase, but decrease. In WEBnm@ a similar movement can be seen in mode 8 with just a few residues moving.

Mode 9

<figure id="mode9_gif">

Representation of the PAH (pdb 1J8U) movement calculated by elNémo.

</figure> <figure id="mode9_matrix">

Matrix showing the maximal distance fluctuation of PAH (pdb 1J8U). If the distances decrease they are plotted in red, whereas increasing distances are shown in blue, but only if they are under the 10% strongest distance changes.

</figure>

...

Mode 10

<figure id="mode10_gif">

Representation of the PAH (pdb 1J8U) movement calculated by elNémo.

</figure> <figure id="mode10_matrix">

Matrix showing the maximal distance fluctuation of PAH (pdb 1J8U). If the distances decrease they are plotted in red, whereas increasing distances are shown in blue, but only if they are under the 10% strongest distance changes.

</figure>

...

Mode 11

<figure id="mode11_gif">

Representation of the PAH (pdb 1J8U) movement calculated by elNémo.

</figure> <figure id="mode11_matrix">

Matrix showing the maximal distance fluctuation of PAH (pdb 1J8U). If the distances decrease they are plotted in red, whereas increasing distances are shown in blue, but only if they are under the 10% strongest distance changes.

</figure>

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References

<references/>