I think this was done by the default refine.py script. Or?



On Oct 26, 2016, at 10:26 PM, Clore, Marius (NIH/NIDDK) [E] wrote:

> The other thing you need to do if you're going to fit NH RDCs together with 
> X-ray data is make sure you're in torsion angle dynamics mode so that the 
> covalent geometry is fixed. Otherwise you can always move the proton of the 
> NH bond to fit the RDCs perfectly and of course this will have absolutely no 
> impact on the agreement with the X-ray data as the X-ray scattering doesn't 
> see protons.
> 
> 
> -------------------------------
> G. Marius Clore, MD, PhD
> NIH Distinguished Investigator
> Chief, Protein NMR Section
> Laboratory of Chemical Physics
> Bldg 5, Room B1-30I
> NIDDK, National Institutes of Health
> Bethesda, MD 20892-0520
> Tel: (301) 496 0782
> Fax: (301) 496 0825
> e-mail: [email protected]
> web: http://spin.niddk.nih.gov/clore (Clore lab homepage)
>        http://www.nasonline.org/member-directory/members/20033168.html 
> (National Academy of Sciences web page)
>        http://www.ae-info.org/ae/User/Clore_G._Marius (Academia Europaea web 
> page)
> ________________________________________
> From: Gabriel Cornilescu [[email protected]]
> Sent: Wednesday, October 26, 2016 3:39 PM
> To: Emmanouilidis, Leonidas
> Cc: [email protected]
> Subject: Re: [Xplor-nih] refine.py script handling off RDCs
> 
> Hi Leonidas,
> over fitted
> I think the refinement worked fine, it's just indeed overfitted single
> set of NH RDCs. It's easy to get the gb1 backbone to fit a single set of
> NH RDCs by small torsion angle changes (see attached plot
> refine_0_vs_start_model.png). You can see how the backbone was locally
> deformed at residue Glu-15 to fit the RDC you changed from -9 to +5 Hz.
> 
> If you fit the original set of RDCs to one of the structures you
> calculated, you'll see that xplor fitted very well the original RDCs and
> that the ones you altered are large outliers:
> calcTensor -aveType sum -normType none -plot -showRDCs
> tmv107_nh_orig.tbl refine_0.sa
> (see attached refine_0_fit_orig_rdc.png)
> 
> Adding the bicelle NH RDCs (attached as gb1_two_media.tar.gz) will
> substantially reduce over fitting either set (rmsds are around 0.8-1.0 Hz):
> calcTensor -aveType sum -normType none -plot -showRDCs tmv107_nh.tbl
> refine_0.sa
> (refine_0_with_bicelle_rdc.png attached). Again Lys-31 (with RDC changed
> from +8 to -8Hz) stands out as an outlier.
> 
> 
> The weight of the RDCs was high in that example to enforce agreement
> with lots of RDCs in two media (including lots of small long-range ones,
> with larger exp. errors).
> 
> When using a single set in a single medium you therefore need to reduce
> the weight of the RDCs until the scatter in the calculated structures
> matches the experimental errors, i.e. change:
> rampedParams.append( MultRamp(0.05,5.0, "rdcs.setScale( VALUE )") )
> 
> to something like:
> rampedParams.append( MultRamp(0.05,0.2, "rdcs.setScale( VALUE )") )
> 
> So basically you can fit efficiently your X-ray structure to a set of
> RDCs (but make sure you don't over-fit it). If you have independent sets
> of RDCs you can use them initially to cross validate your results and
> later include them all in the refinement.
> 
> Hope it makes sense,
> Gabriel
> 
> On 10/26/2016 09:16 AM, Emmanouilidis, Leonidas wrote:
>> Dear Dr Cornilescu,
>> 
>> please find attached the folder as you asked. If you need anythin else 
>> please let me know.
>> 
>> kind regards,
>> Leonidas Emmanouilidis
>> 
>> 
>> 
>> ________________________________________
>> From: Gabriel Cornilescu <[email protected]> on behalf of Gabriel 
>> Cornilescu <[email protected]>
>> Sent: Tuesday, October 25, 2016 8:53 PM
>> To: Emmanouilidis, Leonidas
>> Cc: [email protected]; Charles Schwieters
>> Subject: Re: [Xplor-nih] refine.py script handling off RDCs
>> 
>> If you can tar and zip the folder containing your test (except the huge
>> xplor output file) and email it to me I will take a look.
>> 
>> 
>> On 10/25/16 10:24 AM, Emmanouilidis, Leonidas wrote:
>>> thank you very much for the suggestion.
>>> 
>>> I have tried as you suggested, having random RDC values for residues 
>>> 16,29,31,39,48,53 of gb1. The result was the same. Converence with perfect 
>>> correlation obs/calc without really violations.
>>> 
>>> 
>>> 
>>> 
>>> 
>>> 
>>> ________________________________________
>>> From: [email protected] [[email protected]] on behalf of Gabriel 
>>> Cornilescu [[email protected]]
>>> Sent: Monday, October 24, 2016 11:18 PM
>>> To: Emmanouilidis, Leonidas
>>> Cc: [email protected]; Charles Schwieters
>>> Subject: Re: [Xplor-nih] refine.py script handling off RDCs
>>> 
>>> That doesn't tell much,  it's equivalent to having a 6% larger alignment 
>>> tensor and the fit has to be identical. Try to either scramble a few 
>>> assignments or add/subtract a few Hertz from just a handful of RDCs to see 
>>> a difference.
>>> 
>>> On Oct 24, 2016 3:52 PM, "Emmanouilidis, Leonidas" 
>>> <[email protected]<mailto:[email protected]>> wrote:
>>> by random I mean addition of 6Hz to all HN-N rdcs.
>>> 
>>> 
>>> 
>>> 
>>> On Oct 24, 2016, at 10:43 PM, Gabriel Cornilescu wrote:
>>> 
>>> 
>>> When you say random,  are you scrambling the assignments,  changing the RDC 
>>> values randomly by 6%, or changing their associated errors?
>>> 
>>> On Oct 24, 2016 3:30 PM, "Emmanouilidis, Leonidas" 
>>> <[email protected]<mailto:[email protected]>> wrote:
>>> This is relative simple.
>>> If one runs the tutorial-based gb1 RDC refinement protocol (refine.py) but 
>>> with hn RDCs values completely random (+6Hz noise to each), the outcome is 
>>> a seemingly successful refinement with no errors.
>>> I did the test using just the hn RDCs.
>>> 
>>> 
>>> 
>>> 
>>> 
>>> On Oct 24, 2016, at 10:11 PM, Charles Schwieters wrote:
>>> 
>>>> Hello Leonidas--
>>>> 
>>>>> while I am trying to refine a crystal structure with RDCs using the
>>>>> refine.py script, I came across a weird result.
>>>>> 
>>>>> I had near perfect correlation between observed and calculated RDCs
>>>>> values, which was fishy. After addition of 5Hz systematic noise to all
>>>>> RDCs, i still had perfect correlation and nice convergence with no
>>>>> violations(!). Initially i thought that there was something wrong with
>>>>> my experimental setup (since i only used RDCs+dihedrals restrains),
>>>>> but I had exactly the same result when I changed also the gb1 tutorial
>>>>> RDCs values.
>>>>> So to sum it up, I used the tutorial script (refine.py) and input
>>>>> files for RDC refinement, regardless of how much I alter the RDCs
>>>>> values (i tried up to +6Hz noise addition) I get always nice
>>>>> convergence, perfect correlation obs/calc with no violations.
>>>>> 
>>>>> Is this how it should be or do I miss/mess somthing?
>>>>> 
>>>> Not sure what's going on- we'll need more details.
>>>> 
>>>> best regards--
>>>> Charles
>>> _______________________________________________
>>> Xplor-nih mailing list
>>> [email protected]<mailto:[email protected]>
>>> https://dcb.cit.nih.gov/mailman/listinfo/xplor-nih
>>> 
>> --
>> 
>> Thanks,
>> Gabriel
>> 
>> https://sites.google.com/a/wisc.edu/gabrielc/
>> 
> 
> 


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