Changes

httphttps://threadsourceforge.gmane.orgnet/p/gmane.science.nmr.-relax.user/1552mailman/message/36569608/

== Text The Question ==Question

'''I wonder if it is Is possible to modify the nmr-use relax programme so that I can do to perform a model-free analysis with using only relaxation data from only one collected at a single magnetic field strength? Alternatively, do you know of any programme (that can be installed on Windows) that can do such analysis?'''

The subject of single field strength data has been discussed numerous times on this mailing list. <br>It answer is recommended to read previous responses to questions relating to single field strength data, and look the other messages in those threads. <br>You will find these discussions quite informative and highly detailed:yes!

#- Martin Ballaschk: http://thread.gmane.org/gmane.science.nmr.relax.user/1409/focus=1438#- Shantanu Bhattacharyya: http://thread.gmane.org/gmane.science.nmr.relax.user/1367/focus=1369#- Mengjun Xue: http://thread.gmane.org/gmane.science.nmrThe subject of single field strength data has been discussed numerous times on this mailing list.relax It is recommended to read previous responses to questions relating to single field strength data, and look the other messages in those threads.user/1276/focus=1277#- Fernando Amador You will find these discussions quite informative and highly detailed: http://article.gmane.org/gmane.science.nmr.relax.user/84#- Shantanu Bhattacharyya: http://thread.gmane.org/gmane.science.nmr.relax.user/1086/focus=1087#- Dhanasekaran Muthu: http://thread.gmane.org/gmane.science.nmr.relax.user/1152/focus=1153#- Vitaly Vostrikov: http://thread.gmane.org/gmane.science.nmr.relax.user/1147/focus=1150#- Aldino Viegas: http://thread.gmane.org/gmane.science.nmr.relax.user/1127/focus=1128#- Pierre-Yves Savard: http://thread.gmane.org/gmane.science.nmr.relax.user/724/focus=725#- Keith Constantine: http://thread.gmane.org/gmane.science.nmr.relax.user/513/focus=517#- Clare-Louise Evans: http://thread.gmane.org/gmane.science.nmr.relax.user/326/focus=332#- Hongyan Li: http://thread.gmane.org/gmane.science.nmr.relax.devel/694/focus=701

These will have lots of additional information{| class="wikitable sortable"|-! Person! Message date! Message ID|-| [https://sourceforge. This is just a selection of possibly the most useful messagesnet/p/nmr-relax/mailman/message/36569855/ Danyun Zeng]| {{#time: Y-m-d H:i:s|Wed, 28 Jan 2015 10:40:23 +0100}}| <small><CAED9pY-m5YEjN6KUX88s_yXLpY1BCudUaVvWWmC0U6WkteDnPA@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36569841/ Sean Leo Moro]| {{#time: Y-m-d H:i:s|Fri, 12 Dec 2014 09:24:51 +0100}}| <small><CAED9pY9eAa7B+pC2+RU_pTXWR14fgtiMAiJdQ7rKw+aY6mALaA@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36569491/ Navratna Vajpai]| {{#time: Y-m-d H:i:s|Tue, 30 Apr 2013 17:32:21 +0200}}| <small><CAED9pY-JcYpQtVpMe2dQf_iLvztQzVue=2d0mEQzYYnaYcRpnA@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36569422/ Shantanu Bhattacharyya]| {{#time: Y-m-d H:i:s|Mon, 7 Jan 2013 11:29:28 +0100}}| <small><CAED9pY_aUzPH0OkZhTc2H=trV1VZ074XMcfT8SHYmKH5Bq6T3Q@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36569341/ Mengjun Xue]| {{#time: Y-m-d H:i:s|Thu, 6 Sep 2012 14:14:19 +0200}}| <small><CAED9pY_R8s31My1w19uh5ss7Cjhh6WJLEs62sUUHsF8SxeEc7g@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36569242/ Fernando Amador]| {{#time: Y-m-d H:i:s|Fri, 11 May 2012 09:34:27 +0200}}| <small><CAED9pY-gtfP__28VpkKgGgRVPAST0S0_Q+Hi94Zre0N=NfVLWg@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36569074/ Dhanasekaran Muthu]| {{#time: Y-m-d H:i:s|Tue, 31 Jan 2012 15:45:22 +0100}}| <small><CAED9pY8UArGMiEf-3_fCjQrBJYPecu+BCGqkqtcSXwSix4e5cQ@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36569071/ Vitaly Vostrikov]| {{#time: Y-m-d H:i:s|Mon, 23 Jan 2012 19:05:12 +0100}}| <small><CAED9pY8SGxe_rF6RKWmXJwyXjrDhzcPZaw5b-nrkX_Bp+OEYMg@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36569049/ Aldino Viegas]| {{#time: Y-m-d H:i:s|Thu, 22 Sep 2011 10:32:26 +0200}}| <small><CAED9pY-=rnJ6EjMHAr-YDKOpf8JfG0unLP+JmZD-oOaGXL5Org@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36569008/ Shantanu Bhattacharyya]| {{#time: Y-m-d H:i:s|Fri, 27 May 2011 10:16:48 +0200}}| <small><BANLkTim-PG-kZQGK7Fn+4SLXZ4vO-DxkYw@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36568645/ Pierre-Yves Savard]| {{#time: Y-m-d H:i:s|Thu, 8 Jan 2009 17:41:20 +0100}}| <small><7f080ed10901080841p88137d1v8d04321393f12ab1@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36568437/ Keith Constantine]| {{#time: Y-m-d H:i:s|Fri, 21 Mar 2008 21:17:33 +0100}}| <small><7f080ed10803211317k6fb586cfpc305eabbc80a5bf2@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/nmr-relax-users/thread/7f080ed10705071527r77c2dbe9oa180cd8e0bb8e69a%40domain.hid/#msg36568252 Clare-Louise Evans]| {{#time: Y-m-d H:i:s|Tue, 8 May 2007 00:27:59 +0200}}| <small><7f080ed10705071527r77c2dbe9oa180cd8e0bb8e69a@mail.gmail.com></small>|-| [https://sourceforge.net/p/nmr-relax/mailman/message/36570744/ Hongyan Li]| {{#time: Y-m-d H:i:s|Thu, 21 Dec 2006 19:53:51 +1100}}| <small><7f080ed10612210053l751e5fd8k96ee6097f0840849@mail.gmail.com></small>|-|}

These will have lots of additional information. This is just a selection of possibly the most useful messages. You will soon see that this is a complicated topic. Note that relax is capable of performing 100% of the functionality of:

* [[Modelfree4 ]] (with or without the Fast-Modelfree GUI interface)* Dasha[[DASHA]]* [[Tensor2 ]] and* [[DYNAMICS]]

* a) <ol style="list-style-type:lower-alpha"> <li>Find an initial diffusion tensor estimate (you can do this in relax by only using model m0). This requires all non-mobile residues and side chain spins to be excluded, and this can be problematic. See the [d'Auvergne and Gooley, 2008b ] paper at http://dx.doi.org/10.1007/s10858-007-9213-3 for an example of the catastrophic failure that this initial estimate can result in. Or the bacteriorhodopsin fragment of Korzhnev [Orekhov et al., 1999 (http://dx.doi.org/10.1023/a:1008356809071) ] where this complete failure was earlier demonstrated.</li> * b) <li>Optimise all of the model-free models from m0 to m9. This requires high precision optimisation, for a comparison of all the softwares see the [d'Auvergne and Gooley, 2008a ] model-free optimisation paper at http://dx.doi.org/10.1007/s10858-007-9214-2. Only relax and Dasha [[DASHA]] implement the full range of model-free models, though the models m6, m7, and m8 cannot be used if only single field strength data is used (m6 is the original 2-time scale motion model of [Clore et al., 1990]).</li> * c) <li>Eliminate failed models (this is only available in relax). See the [d'Auvergne and Gooley, 2006 ] model elimination paper .</li> <li>Select the best model-free model for each spin system. This again requires precision modern techniques, with the best being AIC model select (see the [d'Auvergne and Gooley, 2003] model-free model selection paper). If you are unaware that ANOVA statistics for model selection (hypothesis testing via chi-squared, F- and t-tests) was abandoned by the field of model selection over 100 years ago (a field which makes the NMR field look very, very small), then you should really look at http:that paper.</li> <li>Optimise the global model. This is the diffusion tensor plus the model-free models for all spin systems.</dxli> <li>Check for convergence (identical chi-squared values to a previous iteration, and not necessarily the last one). If no, then go back to b) and repeat. Note that the chi-squared value can go up significantly between iterations, but this is because the model is simplifying itself at a much faster rate by loosing parameters - it's Occam's razor at work. Again see the [d'Auvergne and Gooley, 2008b] paper for figures demonstrating this. The concept as to what is happening during this combined model-free optimisation and model selection algorithm is described in the [d'Auvergne and Gooley, 2007] paper. It can take up to 20 iterations or more to reach convergence, depending upon the quality of the relaxation data and the 3D structure or the system in study.doi</li> <li>Once steps a-f have been completed for all global models (characterised by the spheroid, prolate spheroid, oblate spheroid, and ellipsoid diffusion tensors), then model selection between the different global models needs to be performed.org</10li> <li>Monte Carlo simulations for error analysis must be performed at the end.1007</s10858li> <li>Elimination of failed Monte Carlo simulations is essential for keeping the errors to reasonable values for certain spin systems. This is also a relax-006-9007-zonly feature (see the [d'Auvergne and Gooley, 2007] model elimination paper).</li></ol>

* d) Select the best model-free model for each spin system. This again requires precision modern techniques, with the best being AIC model select (see the d'Auvergne and Gooley, 2003 model-free model selection paper at http://dx.doi.org/10.1023/A:1021902006114). If you are unaware that ANOVA statistics for model selection (hypothesis testing via chi-squared, F- and t-tests) was abandoned by the field of model selection over 100 years ago (a field which makes the NMR field look very, very small), then you should really look at that paper. * e) Optimise the global model. This is the diffusion tensor plus the model-free models for all spin systems. * f) Check for convergence (identical chi-squared values to a previous iteration, and not necessarily the last one). If no, then go back to b) and repeat. Note that the chi-squared value can go up significantly between iterations, but this is because the model is simplifying itself at a much faster rate by loosing parameters - it's Occam's razor at work. Again see the d'Auvergne and Gooley, 2008b paper at http://dx.doi.org/10.1007/s10858-007-9213-3 for figures demonstrating this. The concept as to what is happening during this combined model-free optimisation and model selection algorithm is described in the d'Auvergne and Gooley, 2007 MolBiosyst paper at http://dx.doi.org/10.1039/b702202f. It can take up to 20 iterations or more to reach convergence, depending upon the quality of the relaxation data and the 3D structure or the system in study. * g) Once steps a-f have been completed for all global models (characterised by the spheroid, prolate spheroid, oblate spheroid, andellipsoid diffusion tensors), then model selection between thedifferent global models needs to be performed. * h) Monte Carlo simulations for error analysis must be performed at the end. * i) Elimination of failed Monte Carlo simulations is essential for keeping the errors to reasonable values for certain spin systems. This is also a relax-only feature (see the d'Auvergne and Gooley, 2007 model elimination paper athttp://dx.doi.org/10.1007/s10858-006-9007-z). These steps must be implemented independently of which software you use, as NONE implement the full protocol. Note however that the protocol I developed (in the [d'Auvergne and Gooley, 2007 ] theory paper at http://dx.doi.org/10.1039/b702202f and the [d'Auvergne and Gooley, 2008b ] paper at http://dx.doi.org/10.1007/s10858-007-9213-3) is fully implemented in relax, however this required multiple field strength data.

essential to collect data at multiple field strengths, otherwise it can be sometimes impossible to distinguish between the anisotropic part of the Brownian tumbling of the molecule and internal motion - specifically due to the NH vectors in secondary structure elements all pointing in a similar direction. I have a much better explanation, as well as citations to all the relevant literature in:[d'Auvergne and Gooley, 2007]. In this paper, you will see reviewed both the artificial nanosecond motions of the [Schurr et al., 1994] paper and the artifical [[Rex|R_ex]] motions of the [Tjandra et al., 1995] paper. === Recommendation ===

* d'Auvergne E. J.Finally, you will probably find it much easier to spend the 7-8 days collecting data at another field strength than to implement the [[#Protocol|protocol]] in a relax, [[Modelfree4]], Gooley P. R. or [[DASHA]] script (2007or via multiple iterations of the GUI programs). Set theory formulation , as well as study all of the model-free problem and relevant literature to understand all of the diffusion seeded model-free paradigmtypes of failures than only occurs with single field strength data. Mol. Biosyst With multiple field strength data you can perform [https://gna.org/users/semor Sebastien Morin's] consistency testing analysis in relax[Morin and Gagné, 32009] (7see http://www.nmr-relax.com/manual/Consistency_testing.html), 483. That way you can see if your per-experiment temperature calibration andper-494. experiment temperature control techniques have works sufficiently well (http://dxwww.doinmr-relax.orgcom/manual/10Temperature_control_calibration.html) and if you have used long enough recycle delays. Collecting data at a second field would probably save you significant amounts of time, and has the additional benefit that it would guarantee that the dynamics you see at the end will be real.1039 I cannot emphasize enough how important it is to collect data at multiple fields, most importantly the NOE and R<sub>2</b702202f)sub> data.

Finally, you will probably find it much easier to spend the 7-8 days collecting data at another field strength than to implement the protocol of steps a-i in a relax, Modelfree4, or Dasha script (or via multiple iterations of the GUI programs), as well as study all of the relevant literature to understand all of the types of failures than only occurs with single field strength data. With multiple field strength data you can perform == See also ==[[httpsCategory://gna.org/users/semor Sebastien Morin'sModel-free_analysis]] consistency testing analysis in relax (http://dx.doi.org/10.1007/s10858-009-9381-4 and http://www.nmr-relax.com/manual/Consistency_testing.html). That way you can see if your per-experiment temperature calibration andper-experiment temperature control techniques have works sufficiently well (http://www.nmr-relax.com/manual/Temperature_control_calibration.html) and if you have used long enough recycle delays. Collecting data at a second field would probably save you significant amounts of time, and has the additional benefit that it would guarantee that the dynamics you see at the end will be real. I cannot emphasize enough how important it is to collect data at multiple fields, most importantly the NOE and R2 data.