Gaucher Disease: Task 10 - Normal mode analysis

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Revision as of 09:56, 4 September 2013 by Gerkej (talk | contribs) (Domains)

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lab journal

With normal mode analysis (NMA), you are able to simulate or analyse the natural resonant movements of proteins. There are two different webserver available to do a NMA, WEBnm@ and ElNemo. They provide the following information.

WEBnm@

  • Deformation energy
  • atomic fluctuations
  • correlation matrix
  • atomic displacement

ElNemo

  • amplitudes that were applied in the normal mode perturbation as DQMIN(DQSTEP)DQMAX (perturbation)
  • animations of the top five modes in GIF format (small/large)
  • distance fluctuations between all C-alpha atoms (CA-vari)
  • RMSD with respect to the reference structure
  • visualization of the mean square displacement of all C-alpha atoms associated with a given mode (<R2>)
  • frequency of a mode
  • collectivity of a mode


WEBnm@

WEBnm@ uses only alpha-carbon atoms in the models for the normal mode analysis.

Movements

<figtable id="energy">

Mode Deformation Energy Visualisation Movements
7 174.43
Mode 7
hing-moving
8 251.61
Mode 8
9 344.99
Mode 9
10 759.13
Mode 10
equally breathing of the whole structure
11 1099.96
Mode 11
Five best values of the deformation energy for the lowest-frequency non-trivial modes.

</figtable>

Domains

Motions of corelated residues of Glucocerebrosidase.

The Glucocerebrosidase shows a domain definition according to their chains in the vsualization of the corelated residue motion map on the right. Within the chains, which are identical, a very big domain and very small domain (<100 residues) at the end of the chains can be seen. While the the first consists of a high number of helices and a few sheets, the latter one includes only a few sheets. All domain databases agree with each other that the bigger domain has a glycosidic characteristics. However, they differ in their information about the second domain. While PFAM neglects a second domain, CATH classifies it as an alpha-mannosidase II and SCOP identifies a beta-glycanases. A correlation of motions between residues at the beginning and the end of a chain can be observed. Between the chains there is only a slight movement corrrelation observable. Some residues in the middle of one chain correlate with a few other residues at the beginning of the other chain.

The sequence forms a tube like structure, whereas residues show only correlations with residues that have maximum sequence distance of ~100. However there seems a to be a movement correlation between residues at the begining and the end of the sequnce. As the structure forms a curve, both ends of "tube" are dependent of each other in their movements. The structure shows a different characteristics in different parts of the "tube". One part contains all helices, is less flexible and slower in its motion than the smaller part which has only sheets (can only be seen as loops in <xr id="energy"/>). But although, this sound like a description of two different domains, the Glucocerebrosidase consists only of one domain by considering correlated motions.

As chain A and B are identical, the following domain definition concentrates on one domain: PFAM

  • 1 domain
  • PF02055: Glycoside hydrolase family 30

CATH

SCOP

  • 2 domains
  • b.71.1.2: Composite domain of glycosyl hydrolase families 5, 30, 39 and 51
  • c.1.8.3: beta-glycanases

ElNemo

ElNemo uses also only the C-alpha atoms of the structure for normal mode analysis, therefore it takes only the ATOM record from the PDB file, ignoring the HETATM record of a ligand. As we do not have a structure completely without a ligand, but only structures with different not native ligands (hier kommt der Name von unserem Liganden), we do not have structures with different conformations. Therefore, we could not do the option of calculation of normal modes with two different structures. We ran ElNemo with our reference structure 1OGS.

100 modes were calculated. We analyze the best five best modes, i.e. with lowest frequency and the highest collectivity of the motions. B-factor analysis yielded correlation of 0.662 for 1006 C-alpha atoms.

<figtable id="elnemo_modes">

Mode Animations Description
a b c
7 Mode7 1.gif Mode7 2.gif Mode7 3.gif TODO
8 Mode8 1.gif Mode8 2.gif Mode8 3.gif TODO
9 Mode9 1.gif Mode9 2.gif Mode9 3.gif TODO
10 Mode10 1.gif Mode10 2.gif Mode10 3.gif TODO
11 Mode11 1.gif Mode11 2.gif Mode11 3.gif TODO
Five lowest-frequency modes for the structure 1OGS created by ElNemo (cutoff used to identify elastic interactions=10).

</figtable>


Sources

WEBnm@:
WEBnm@ server
ElNemo:

  1. ElNemo server
  2. K. Suhre & Y.H. Sanejouand, ElNemo: a normal mode web-server for protein movement analysis and the generation of templates for molecular replacement. Nucleic Acids Research, 32, W610-W614, 2004.
  3. K. Suhre & Y.H. Sanejouand, On the potential of normal mode analysis for solving difficult molecular replacement problems. Acta Cryst. D vol.60, p796-799, 2004 © International Union of Crystallography.