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@

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.

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Mode 7

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

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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

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

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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

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

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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

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

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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

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

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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

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

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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 ...

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

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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

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

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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.