Normal mode analysis
Contents
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Introduction
NMA (normal mode analysis) is a time-independent apprach to simulate low-frequency motions and vibrations of protein. These simulation are all based on the harmonic approximation and therefore ignore the influence of the solvent. The proteins are seen as models made out of springs and point masses, which are connected and represent the interatomic forces. Simulation done this way are very easy to do, but are no more than a slight insight into the protein flexibility.
Task?
For each server, analyze at least the lowest five normal modes.
- 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”…
- Can you observe notable differences between the normal modes calculated by different servers?
- Out of the servers, chose one or two favorites and discuss the results of these in more detail. Why do you like these?
- 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?
Parameters
- If possible, use a cutoff for Cα atom pairs of 15 Å.
- Calculate the 10 lowest-frequency normal modes (the six zero modes have to be considered for a few applications).
- In most cases you can upload the original .pdb file from the Protein Data Bank. In some cases, however, you can upload only the structure itself (ATOM lines of the .pdb file).
WEBnm@
WEBnm@ is a webserver based application that allows computation and low-frequency analysis of normal nodes of proteins. This computation is fully automated and only different types of results are presented to the user.
Webserver:
Input:
- 1a6z - all chains
Result:
Discussion:
All animated gifs have to be created the hard way, frame after frame, because WEBnm@ does not allow the concurrent saving of more than one frame.
The Normalized Squared Atomic Displacements (nsad) plots show the vibrations according to the amino acid position.
Except for mode 11 there is no special movement inside the alpha helix of chains A and C. The movement is almost everytime between the chains or inside/around the beta strands of chain B and D. This behaviour is also visible by analyzing the plots; the regions of low movement are always around the chains A and C with their corresponding alpha helices and the high movement regions lies within the beta strands of chain B and D.
The movement/vibrations can be described mostly as repulsive or flattening, stretching and twisting.
There seems to be some strange behaviour at figure 4.2 mode 10; it is slighty twitching and we do not know why. Maybe it is because of a wrong frame or some other aspect of visual glitches, we will check that again, if there is time.
ElNemo
ElNémo is a webserver based to work with the Elastic Network Model. It calculates and analyses low-frequency normal modes of proteins.
Webserver:
Input:
- 1a6z
Result:
Discussion:
For all generated models the vibrations are shown in three different perspectives.
The Movement/Vibrations are very similar to these obtained by WEBnm@. There is almost no movement inside the alpha helices of chain A and C and much movement inside and outside the the beta strands of chain B and D. Vibrations between chains can also be observed but these are mostly between A+C and B+D because they form a subunit.
Anisotropic Network Model web server
The Anisotropic Network Model web server uses the fast approach anisotropic network model (elastic network) to calculate the global modes.
Webserver:
Params:
- distance weight: 3
Result:
Discussion:
oGNM – Gaussian network model
Webserver:
Input:
- 1a6z
Params:
- cutoff: 15 Å
Result:
NOMAD-Ref
Webserver:
Params:
- distance weight: 3.0
- cutoff: 15 Å
Result:
Discussion:
All-atom NMA using Gromacs on the NOMAD-Ref server
Webserver:
Params:
- All-atom calculations are only supported for small proteins of up to 2,000 atoms. Use for example BPTI, PDB entry: 1BPT. Upload a .pdb file that contains only the ATOM lines of the original .pdb file. You can also choose another small protein for the all-atom NMA.
- set the temperature to 600K and 2000K
- you can visualize the modes with PyMol or VMD.
- Compare the all-atom NMA of BPTI (or your chosen protein) with an elastic network calculation, e.g. NOMAD-Ref.
Used:
- 1a6z?
