Hi,
I've been thinking about this one for a while, but I don't know
exactly what the problem is. I have a few ideas that may help though.
This could either be some type of interesting dynamics, or be caused
by something a bit more sobering.
Firstly though, it is worth comparing the local tm model to the best
of the global diffusion tensor models (the ellipsoid). It could be
that if the AIC values are similar, then the local tm model and the
global diffusion model are statistically similar and that it would be
safe to go with either. In this case, it is worth very carefully
comparing the description of the internal dynamics. For this, do not
compare selected models - that is not what is of interest. It should
be the overall picture of the dynamics reported by the parameters.
For example if Rex is statistically close to zero then, from the
perspective of the internal motions, models m2 and m4 are the same.
Assuming that the local tm global model is significantly better than
the other models, another option could be that you have very
interesting global concerted dynamics occurring in the molecule. This
would mean that the standard single global diffusion model (sphere,
spheroid, or ellipsoid) is insufficient to describe these motions.
This is what the hybrid models in relax were designed for, but maybe
these don't describe certain large scale motions well enough (hence
your use of these didn't resolve the problem). These aren't a proper
mathematical solution to the complex physics of coupled diffusion
processes and hence may be insufficient.
It might be worth trying the normal model-free analysis of starting
with the diffusion tensor, rather than my new technique which starts
with the internal dynamics, to see if you end up with a different
result. It could be that the new technique in the full_analysis.py
script is somehow failing, although I doubt that will be the case.
The oscillation you see in point 3 is found by using Art Palmer's
Modelfree program as well with a standard analysis - this was one of
the motivators for me to start looking into and fixing problems with
model-free analysis - but it is inherent to the iterative procedure
required for convergence. Have you tried the analysis with Modelfree
or Dasha? And if so, how do the chi-squared and AIC values compare?
Alternatively, the reason could be quite simple. It could possibly be
that the structure you have used in the analysis is not accurate
enough. If it is a crystal structure, maybe it doesn't represent the
solution structure well. The analysis is highly dependent upon the XH
bond vector orientations, and if this is slightly out it could cause a
bias and the introduction of artificial motions (either Rex or
nanosecond motions). It will also affect the determination of the
diffusion tensor. These artificial motions are unlikely to be present
in the local tm model though, so this is a good check.
The Rex in the ellipsoid model is an indication that something could
be wrong with the global model. Whether it is interesting large scale
motions which are insufficiently described by the ellipsoid, whether
the technique cannot find the real solution, or whether this is caused
by structural inaccuracies, that I cannot tell. Is the structure of
the protein released? What is the system which is being studied?
What are the AIC values like for each global model? Anyway, hopefully
one of these ideas may be of help in sorting out the problem.
Regards,
Edward
On Mon, May 5, 2008 at 9:23 PM, Sébastien Morin
<sebastien.morin.1@xxxxxxxxx> wrote:
Hi,
I am currently using relax with the full_analysis.py script.
I face several problems for which I can't find any solution...
1.
With all my data (230 residues at 3 fields, for a total of 2070
observables), the best diffusion model is the local tm. This is not
normal as this protein is globular. Hence, the C-terminus residues have
really high chi2 values... Thus, when excluding the C-terminus, the best
diffusion model is still the local tm. Maybe some other residues are
highly flexible and should be rejected... Maybe also some residues have
bad data... What is a good strategy to find residues I should exclude
from my analysis ?
2.
When I look at optimized results from the ellipsoid runs (second best
choice after local tm), I see lots (~ 50 % residues) of Rex, which is a
bit anoying... The diffusion tensor may not be well optimized... This
may be related to problem 1...
3.
In different situations, some runs (prolate or ellipsoid, i.e. the
diffusion tensor that should best describe my system) never converge and
oscillate between 2 or more AIC values. Some residues oscillate between
2 or more models, but these residues are not special as to their
relaxation data or position in the protein...
Consistency testing and reduced spectral density mapping show that my
data are of good quality and are consistent with each other...
I tried with different structures (crystal structure with added protons,
MM snapshots), but always got the same kind of results...
I tried several hybrids (with no C-ter, with no C-ter and several loops,
etc), but always got the same kind of results...
Also, chi2 values are quite high for most residues (5-20 on average)...
What should I do now ? Do you have any idea ?
Thanks a lot for any help or idea !!!!!!!
Exhausted Séb
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Re: Full analysis issue