Thank you Edward,

Really appreciate the help and advice.

Best regards,
Andras



> On Apr 18, 2019, at 11:33 AM, Edward d'Auvergne <[email protected]> wrote:
> 
>        External Email - Use Caution        
> 
>> Temperature control:
>> I did have a recent temperature calibration in place, but did not calibrate 
>> when setting up the experiment.
>> I probably should have done that.
>> 
>> I did use heat compensation blocks during the experiment, but did not do 
>> single scan or experiment interleaving.
>> 
>> Is there a way to account for this in relax, or is re-recording of the data 
>> the only remedy?
> 
> As I mentioned to Thibault, book some more NMR time (~2 hours) and
> rerun mini-versions of your experiments with MeOH or methylene glycol
> standards.  Then measure the temperature of the experiment.  But if
> you did minimally use fid interleaving for all experiments (single
> scan interleaving is really only needed for the R2), then you will
> have daily temperature fluctuations affecting your data in a
> significant way.  There is a publication on this effect by Wüthrich, I
> think.
> 
> 
>> Single diffusion tensor estimate:
>> I looked through the local tm model results and they appear to be all over 
>> the place, although the relaxation behavior of the protein predicts that 
>> they should be rather similar.
>> chi2 values were generally in the double to three (hundreds) digit region. 
>> The model selection changes from residue to residue.
>> I don't believe that this sample dimerizes, but have not done a dilution 
>> series yet.
> 
> The local tm models are noisy - it is over-fitting - but the general
> trend in the data should explain the global diffusion tensor selected.
> Was the chi2 value high for the local tm models too?  That would not
> good and might indicate that you have bad data.
> 
> 
>> R1, R2, NOE:
>> All fittings were done in Relax and heights and noise were measured 
>> following recommendations in the relax manual. I also compared fits to 
>> fitting with other methods. The errors and curve fits look ok.
> 
> What about the chi2 values?  Are these high?  If not, that would again
> be a sign of the individual experiments being ok, but that temperature
> calibration and control might be an issue.
> 
> 
>> 13C Coupling:
>> I think I did not formulate this question clearly. My concern was with the 
>> effect of dipolar couplings from 13C carbons on relaxation.
>> There is no question that the scalar coupling must be taken care of at the 
>> experimental level and this is of course what I did.
>> Upon looking into this further, I believe that the effect from the dipolar 
>> couplings should be negligible.
> 
> That is what I understood - the 15N-13C dipolar relaxation.  If you
> have fully labelled 15N and 13C samples, this is actually a
> significant source of relaxation.  Significant in a model-free
> analysis would probably be a contribution of >5%.  There are multiple
> publications on this issue, but unfortunately I cannot remember them
> off the top of my head.  For example there was some work on this for
> analysing DNA.  I know this because there is an abandoned branch of
> relax for handling multi-pole relaxation due to this exact effect in
> nucleic acids.
> 
> Anyway, you should first determine if your data is good or bad.  You
> could try the consistency testing analysis in relax for example.  But
> first carefully check your temperature calibration and control.  And
> also study the literature on 15N-13C dipolar relaxation in fully
> labelled samples.  And, as I mentioned to Thibault, no one gets
> relaxation data measurements correct the first time ;)
> 
> Regards,
> 
> Edward



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