Normal Mode Analysis (PKU)

Short Task Description

This week, we will perform a normal mode analysis of our wildtype protein. We will calculate visualize large coordinate movements to identify e.g. domains and try to watch ligand interaction. For this, we will use the webnm@ and elNemo webservers. See the task description for details, a journal of commands and scripts, if necessary, can be found here.

Normal Mode Analysis

In normal mode analysis (NMA) the protein is modeled as harmonically oscillating system to e.g. describe conformational changes. Normal modes are much faster to calculate than a molecular dynamics simulation, especially as usually very few low-frequency modes suffice to describe a proteins motions.<ref name=ElNemo>Karsten Suhre and Yves-Henri Sanejouand; ElNémo: a normal mode web server for protein movement analysis and the generation of templates for molecular replacement. Nucleic Acids Research Volume 32, Issue suppl 2</ref> Often, models do not include the sidechains of a protein so the effect of mutations can not be detected. Also, non-harmonic motions are not observable which limits the insights gained from NMA in comparison to the much more detailed molecular dynamics simulation.

WEBnm@

<figure id="fig:mode7">

Animation of mode 7 from WEBnm@. Original pdb-structure is colored green. BH4 is colored yellow and the Fe2+ ion is colored in red. The mesh represents the model gained from WEBnm@.

</figure> <figure id="fig:mode8">

Animation of mode 8 from WEBnm@. Original pdb-structure is colored green. BH4 is colored yellow and the Fe2+ ion is colored in red. The mesh represents the model gained from WEBnm@.

</figure> <figure id="fig:mode9">

Animation of mode 9 from WEBnm@. Original pdb-structure is colored green. BH4 is colored yellow and the Fe2+ ion is colored in red. The mesh represents the model gained from WEBnm@.

</figure>

elNemo

ElNemo computes ten perturbed models for the first five non-trivial normal modes of the input protein as a standard and perturbations for the lowest 25 modes on request in a separate queue. There is no fixed limit to the size or number of modes but too long running jobs will eventually be killed. The calculation uses a cutoff value to determine which atom-atom interactions are kept in the elastic network model and another parameter to determine how many residues are treated as rigid body to speed up calculation appropriately.

1J8U (without ligand)

Mode 7

<figure id="fig:1J8U_nm7">

The crystal structure of 1J8U in transparent green and the normal mode 7 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U_nm7_fluc">

The relative fluctuations of the C alpha atoms of 1J8U computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 7.

</figure>

Mode 8

<figure id="fig:1J8U_nm8">

The crystal structure of 1J8U in transparent green and the normal mode 8 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U_nm8_fluc">

The relative fluctuations of the C alpha atoms of 1J8U computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 8.

</figure>

Mode 9

<figure id="fig:1J8U_nm9">

The crystal structure of 1J8U in transparent green and the normal mode 9 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U_nm9_fluc">

The relative fluctuations of the C alpha atoms of 1J8U computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 9.

</figure>

Mode 10

<figure id="fig:1J8U_nm10">

The crystal structure of 1J8U in transparent green and the normal mode 10 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U_nm10_fluc">

The relative fluctuations of the C alpha atoms of 1J8U computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 10.

</figure>

Mode 11

<figure id="fig:1J8U_nm11">

The crystal structure of 1J8U in transparent green and the normal mode 11 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U_nm11_fluc">

The relative fluctuations of the C alpha atoms of 1J8U computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 11.

</figure>

1J8U and BH4 ligand

Mode 7

<figure id="fig:1J8U+BH4_nm7">

The crystal structure of 1J8U with the BH4 ligand in transparent green and the normal mode 7 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U+BH4_nm7_fluc">

The relative fluctuations of the C alpha atoms of 1J8U with the BH4 ligand computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 7.

</figure>

Mode 8

<figure id="fig:1J8U+BH4_nm8">

The crystal structure of 1J8U with the BH4 ligand in transparent green and the normal mode 8 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U+BH4_nm8_fluc">

The relative fluctuations of the C alpha atoms of 1J8U with the BH4 ligand computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 8.

</figure>

Mode 9

<figure id="fig:1J8U+BH4_nm9">

The crystal structure of 1J8U with the BH4 ligand in transparent green and the normal mode 9 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U+BH4_nm9_fluc">

The relative fluctuations of the C alpha atoms of 1J8U with the BH4 ligand computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 9.

</figure>

Mode 10

<figure id="fig:1J8U+BH4_nm10">

The crystal structure of 1J8U with the BH4 ligand in transparent green and the normal mode 10 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U+BH4_nm10_fluc">

The relative fluctuations of the C alpha atoms of 1J8U with the BH4 ligand computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 10.

</figure>

Mode 11

<figure id="fig:1J8U+BH4_nm11">

The crystal structure of 1J8U with the BH4 ligand in transparent green and the normal mode 11 movement computed by ElNemo in blue.

</figure> <figure id="fig:1J8U+BH4_nm11_fluc">

The relative fluctuations of the C alpha atoms of 1J8U with the BH4 ligand computed by ElNemo. Red or green dots indicate those residues for which the distance significantly increases or decreases respectively in movement related to mode 11.

</figure>

References

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