Normal Mode Analysis of Glucocerebrosidase

Elastic and Gaussian Network Models

WEBnm@

WEBnm@ is a web-server which provides automated computation and analysis of low-frequency normal modes of proteins. For an input structure file in PDB format, the normal modes are calculated and a series of automated calculations (normalized squared atomic displacements, vector field representation and an animation of the first six vibrational modes). Additional to the single analysis (calculating lowest frequency normal modes for one protein), the server offers a comperative analysis. In this analysis, the normal modes of a set of aligned sequences are calculated and compared. This feature is still under development. <ref>Hollup SM, Sælensminde G, Reuter N. WEBnm@: a web application for normal mode analysis of proteins BMC Bioinformatics. 2005 Mar 11;6(1):52 </ref>

Usage

• Webserver: http://apps.cbu.uib.no/webnma/home
• Input:
  • Single Analysis: structure file in PDB format
  • Comparative Analysis: structure files in PDB format and sequence files in fasta format

Results

Figure 1 to 5 show the first five vibrational modes (modes 7 to 11) calculated with WEBnm@ for the structure of glucocerebrosidase (2NTO). On the left side of each figure the vectors are shown, whereas the movement is illustrated to the right.

Figure 1: Normal Mode 7 calculated with WEBnm@	Figure 2: Normal Mode 8 calculated with WEBnm@
Figure 3: Normal Mode 9 calculated with WEBnm@	Figure 4: Normal Mode 10 calculated with WEBnm@
Figure 5: Normal Mode 11 calculated with WEBnm@

Discussion

ElNémo

ElNémo is a web-server based on the Elastic Network Model. The tool computes, visualizes and analyses low-frequency normal modes of large macro-molecules. Any size of proteins can be treated as ElNémo uses a 'rotation-translation-block' approximation. <ref>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. </ref>

Usage

• Webserver: http://www.igs.cnrs-mrs.fr/elnemo/start.html
• Input:
  • • structure file in PDB format
    • supplementary options for NMA calculation (number of normal modes to be calculated, minimum and maximum perturbation and stepsize between DQMIN and DQMAX)
    • options for computing the eigenmodes (NRBL and cutoff to identify elastic interactions)

Results

Figure 6 to 9 show for each of the five first vibrational normal modes calculated with ElNémo three different perspectives.

Figure 6: Normal Mode 7 calculated with ElNémo	Figure 7: Normal Mode 8 calculated with ElNémo
Figure 8: Normal Mode 9 calculated with ElNémo	Figure 9: Normal Mode 10 calculated with ElNémo
Figure 10: Normal Mode 11 calculated with ElNémo

Discussion

Anisotropic Network Model

The ANM Webserver provides NMA Analysis with the anisotropic network model (ANM) which is an elastic network (EN) introduced in 2000. It is a very fast method which predicts the global modes. The ANM adopts a uniform force constant γ to all springs and nodes are refered as the Cα atoms.<ref>Anisotropic network model: systematic evaluation and a new web interface, Eyal E, Yang LW, Bahar I. Bioinformatics. 22, 2619-2627, (2006)</ref>

Usage

• Webserver: http://ignmtest.ccbb.pitt.edu/cgi-bin/anm/anm1.cgi
• Input:
  • structure file in PDB format or PDB id and chain
  • model
  • cutoff for interaction between Cα atoms in Å
  • distance weight for interaction between Cα atoms

Results

Mode 1	Mode 2	Mode 3	Mode 4	Mode 5
Figure 11: Normal Mode 1 calculated with ANM	Figure 12: Normal Mode 2 calculated with ANM	Figure 13: Normal Mode 3 calculated with ANM	Figure 14: Normal Mode 4 calculated with ANM	Figure 15: Normal Mode 5 calculated with ANM
Inter Distance Analysis
Figure 16a: Distance Matrix Figure 16b: Deformation Energy Overall energy: 27824.672768448	Figure 17a: Distance Matrix Figure 17b: Deformation Energy Overall energy: 42344.496142536	Figure 18a: Distance Matrix Figure 18b: Deformation Energy Overall energy: 43818.992771088	Figure 19a: Distance Matrix Figure 19b: Deformation Energy Overall energy: 85235.1119198879	Figure 20a: Distance Matrix Figure 20b: Deformation Energy Overall energy: 90925.846279128
B-factors/mode fluctuations
Figure 21: B-factors/mode fluctuations	Figure 22: B-factors/mode fluctuations	Figure 23: B-factors/mode fluctuations	Figure 24: B-factors/mode fluctuations	Figure 25: B-factors/mode fluctuations

Mode 6	Mode 7	Mode 8	Mode 9	Mode 10
Figure 26: Normal Mode 6 calculated with ANM	Figure 27: Normal Mode 7 calculated with ANM	Figure 28: Normal Mode 8 calculated with ANM	Figure 29: Normal Mode 9 calculated with ANM	Figure 30: Normal Mode 10 calculated with ANM
Inter Distance Analysis
Figure 31a: Distance Matrix Figure 31b: Deformation Energy Overall energy: 107191.169783064	Figure 32a: Distance Matrix Figure 32b: Deformation Energy Overall energy: 112430.078797944	Figure 33a: Distance Matrix Figure 33b: Deformation Energy Overall energy: 138939.176046648	Figure 34a: Distance Matrix Figure 34b: Deformation Energy Overall energy: 156195.358655472	Figure 35a: Distance Matrix Figure 35b: Deformation Energy Overall energy: 154660.33882932
B-factors/mode fluctuations
Figure 36: B-factors/mode fluctuations	Figure 37: B-factors/mode fluctuations	Figure 38: B-factors/mode fluctuations	Figure 39: B-factors/mode fluctuations	Figure 40: B-factors/mode fluctuations

Cα anisotropic temperature factors as ellipsoids
purely computational		refined by experimental b-factors
Rastep	Povscript	Rastep	Povscript
Figure 41	Figure 42	Figure 43	Figure 44

Discussion

References

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