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Revision as of 20:10, 8 August 2011
Contents
WEBnm@
Background information
WEBnm@ provides two different modes:
Single Analysis:
The Single Analysis calculates the lowest frequency normal modes of the given protein and offers different types of calculations to analyse the modes that were calculated. The force field used for the Normal Modes Calculations is the C-alpha force field It uses only the Calpha atoms of the protein which are assigned the masses of the whole residue they represent.
The different types of calculation are:
- deformation energies of each mode
- calculation of normalized squared atomic displacements (results are provided for each low frequency mode, either as raw data or as plots with displacement vs. residue number)
- interactive visualization of the modes using vector field representation or vibrations
Comparative Analysis (beta version;)
The Comparative Analysis calculates and compares the normal modes of a set of aligned protein structures. This tool is still under development. It also provides three types of calculations:
- Deformation Energy profiles
- Atomic Fluctuation profiles
- Conformational Overlap Comparison
Input:
- Single Analysis: structure file in the pdb format
- Comparative Analysis: a file containing the sequence alignment of the proteins which should be compared and a protein structure file for each of the proteins. The alignment file needs to be written in the Fasta format, and the header line of each sequence should contain the name of the structure file as first field, and the chain in the last field.
Results
Below are the values of the deformation energy for modes 7 to 20
| Mode Index | Deformation Energy |
|---|---|
| 7 | 292.36 |
| 8 | 401.29 |
| 9 | 603.95 |
| 10 | 757.28 |
| 11 | 848.99 |
| 12 | 989.93 |
| 13 | 1745.19 |
| 14 | 2675.54 |
| 15 | 2999.49 |
| 16 | 3341.82 |
| 17 | 3572.19 |
| 18 | 3685.84 |
| 19 | 4103.34 |
| 20 | 4925.43 |
WEBnm@ visualised the normalized squared atomic displacements for the first six modes (modes 7 to 12).
The square of the displacement of each Calpha atom, normalized so that the sum over all residues is equal to 100.
Highest values correspond to the most displaced regions. On the plots, one should look for cluster of peaks, those identify significantly big regions. Isolated peaks reflect local flexibility and are not relevant.
| mode 7 | mode 8 | mode 9 | mode 10 | mode 11 | mode 12 |
|---|---|---|---|---|---|
ElNemo
Background information
Input
The input for ElNemo is a protein structure in PDB format. But of this PDB file only the residues that are encoded by ATOM are used in the calculations. The other residues are not taken into account. If there are other residues which should be used in the calculations they have to be encoded by ATOM. Additionally there are a lot of options which can be choosen.
Output
- properties of the first 100 lowest frequency modes (frequency, collectivity of atom movement, overlap of each mode with the observed conformational change (if two conformations are available) and its corresponding amplitude)
- 3D animations from three orthogonal viewpoints in large and small sizes
- Comparison of a normal mode perturbed structure and a second conformations in terms of RMSD and number of residues that are closer than 3A can be done
- cross plot where the analysis of distance fluctuations between all CA atoms is shown (red and blue dots indicate the residues for which the distance changes significantly in movement)
Results
CA distance fluctuations for the six modes
| mode 7 | mode 8 | mode 9 | mode 10 | mode 11 | mode 12 |
|---|---|---|---|---|---|
ElNemo prepared different views from three orthologuous viewpoints with MolScript for each mode.
Mode 7:
Mode 8:
Mode 9:
Mode 10:
Mode 11:
Mode 12:
Anisotropic Network Model web server
oGNM – Gaussian network model
results here: [[1]]
NOMAD-Ref
The NOMAD <ref>[[2]]</ref> server provides a lot of information and options. The interface is quite user friendly as all available parameter choices are explained in detail and there is also the runtime listed for an example NMA, which can be used to estimate the runtime for our own jobs.
The following parameters can be set:
- Number of modes to calculate
- As specified in the task description we wanted to obtain 10 modes. NOMAD does six zero modes which are just translation and rotation. Therefore we set the number of modes to calculate to 16.
- Distance weight parameter
- This parameter is used to introduce a smoother cutoff value that in the original Tirion model. All distances are weightend by exp(-(d_ij/d)^2), where d is the distance weight parameter. As proposed by NOMAD a distance weight parameter of 3Å is well suited for CA-only models. As we are doing no all-atom calculation, the distance weight parameter was set to 3.0Å.
- Cutoff to use for mode calculation
- The cutoff describes which pairs of atomes are linked by a spring of universal length according to the Tirion model (Elastic Network Model). The cutoff was set to 15Å.
- Average Rmsd in output trajectories
- For the average RMSD the default value (3.0) was used.
- Method to use
- Automatic
- Full matrix solver
- Sparse matrix solver
- Here we used the default option, the automatic mode.
The output contains one PDB file and one plot per mode. The plot contains the rmsd per residue, which can be interpreted as the amplitude of movement and which is controlled by the average rmsd of trajectory (input parameter).
What information do the different servers provide? Which regions of your protein are most flexible, most stable? When you visualize the modes (provided by server or using for example PyMol or VMD), try to describe what movements you observe? Hinge-movement, “breathing”…
| mode 1 | mode 2 | mode 3 | mode 4 | mode 5 |
All-atom NMA using Gromacs on the NOMAD-Ref server
In order to do the all-atom NMA we needed an appropriate small molecule that contained not more than 2000 atoms. This small protien was found by searching for "all atom nma". We found a paper <ref>Hetunandan Kamisetty, Eric P. Xing and Christopher J. Langmead: Free Energy Estimates of All-atom Protein Structures Using Generalized Belief Propagation[[3]]</ref>. They used the structure of a hen egg-white lysozyme for an all atom NMA. So we did all the calculations for the corresponding PDB entry 2lyz.
First, we needed to prepare our PDB file. The PDB file for 2LYZ protein contains 1001 atoms in total, all lines not beginning with "ATOM" were removed from the PDB file.
600 K
The following movies show the all-atom NMA for 2LYZ at 600K
| mode 1 | mode 2 | mode 3 |
2000 K
The following movies show the all-atom NMA for 2LYZ at 2000K
| mode 1 | mode 2 | mode 3 |
Comparison to an Elastic Network
Frage: je berechnung eines elastic networks für mode 7, 8 und 9 oder berechnugn eines el networks für "normale" pdb und dann überlagerung mit den modes?
Ich habe jetzt mal für jeden mode (7,8,9) das vorher berechnete network einfach überlagert.
| mode 1 | mode 2 | mode 3 |
Advantages and Disadvantages from NMA and MD
References
<references />
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