Fabry:Normal mode analysis

Tasks and questions

In this task you will analyze your protein structure using elastic network models. You will use two servers to calculate the normal modes:

WEBnm@ and ElNemo

For each server, calculate and analyze the lowest five (to ten) normal modes. If possible (for ElNemo), use a cutoff for C_α atom pairs of 10 Å. Note: ElNemo reads only the ATOM record from the PDB file. If your protein has a ligand which is given as HETATM, you need to change this to ATOM, if it should be accounted for in the normal mode calculation.

• What information do the different servers provide?
• How are the normal modes calculated, that is from which part of the structure? How many normal modes could in principle be calculated for your protein without any cutoff.
• Visualize the modes (provided by server or using for example PyMol or VMD) and describe what movements you observe: hinge-movement, “breathing”…
• Which regions of your protein are most flexible, most stable?
• Can you identify domains for your protein? Compare to the CATH, SCOP and Pfam domains of your protein.
• Can you observe notable differences between the normal modes calculated by the different servers?
• For WEBnm@ try the amplitude scaling and vectors option.
• Try the comparison/upload of second structure option, if: (i) you have PDB structures in different conformations or (ii) your protein has a bound ligand. Then either upload a structure with and one without the ligand, or delete the ligand in your structure. Note: Due to the force field that considers only C_alpha atoms, only changes in the backbone will give results. The model does not resolve changes in side-chain positions or SNPs.
• When your MD simulations are finished, compare the lowest-frequency normal modes with your MD simulation using visualization software, e.g. PyMol or VMD. Can you observe different movements or similar dynamics? If possible, compare an overlay of the lowest-frequency modes to your MD simulation. You can superimpose the normal modes for example in VMD.
• What are the advantages and disadvantages of NMA compared to MD?

VMD (Visual Molecular Dynamics, version 1.9.1) is installed on i12k-biolab01 (type 'vmd' at command line). Here is a VMD tutorial and the documentation.

Wiki review

We will decide next week, which group is reviewing which group for this task.

Here are some other servers:

Anisotropic Network Model web server

oGNM – Gaussian network model

NOMAD-Ref

References

Nathalie Reuter, Konrad Hinsen & Jean-Jacques Lacapère. (2003) Transconformations of the SERCA1 Ca-ATPase: A Normal Mode Study. Biophys J 85(4): 2186–2197.

Siv Midtun Hollup, Gisle Salensminde & Nathalie Reutercorresponding. (2005) WEBnm@: a web application for normal mode analyses of proteins. BMC Bioinformatics 6: 52.

Karsten Suhre & Yves-Henri Sanejouand. (2004) ElNemo: a normal mode web-server for protein movement analysis and the generation of templates for molecular replacement. Nucleic Acids Research 32 (suppl 2): W610-W614.

Silke A. Wieninger, Engin H. Serpersu & G. Matthias Ullmann. (2011) ATP Binding Enables Broad Antibiotic Selectivity of Aminoglycoside Phosphotransferase(3′)-IIIa: An Elastic Network Analysis. J Mol Biol 409(3):450-65.

William Humphrey, Andrew Dalke & Klaus Schulten. (1996) VMD: visual molecular dynamics. J Mol Graph14(1):33-8, 27-8.

The PyMOL Molecular Graphics System, Version 1.5.0.4 Schrödinger, LLC.

WEBnm@

<figtable id="tab:webnma"> In this table are the 6 modes shown, that were calculated by WEBnm@. Depicted is the structure 3HG2, which represents the Human alpha-galactosidase catalytic mechanism with empty active site in cyan and the substrate binding site at position 203 to 207 highlighted in red.

WEBnm@ mode 7	bla
WEBnm@ mode 8	bla
WEBnm@ mode 9	bla
WEBnm@ mode 10	bla
WEBnm@ mode 11	bla
WEBnm@ mode 12	bla

</figtable>