Model-free analysis single field - Revision history

Bugman: Switch to the {{relax developer link}} template to remove dead Gna! links.

2020-10-16T08:46:01Z

Switch to the {{relax developer link}} template to remove dead Gna! links.

Bugman: /* The Question */ Fixes for the mailing list links, and conversion into a sortable wikitable.

2020-01-07T09:32:43Z

The Question: Fixes for the mailing list links, and conversion into a sortable wikitable.

Bugman: /* Reference */ Fix for the primary link.

2020-01-07T08:23:16Z

Reference: Fix for the primary link.

Bugman: /* Warning */ Link to Rex.

2020-01-07T08:18:29Z

Warning: Link to Rex.

Bugman: /* Protocol */ Switch to a lettered list.

2020-01-07T08:15:49Z

Protocol: Switch to a lettered list.

Bugman: Internal links for different softwares.

2015-12-15T16:11:51Z

Internal links for different softwares.

Bugman: Internal links to DASHA.

2015-12-15T15:07:33Z

Internal links to DASHA.

Bugman: /* References */ Switched to a labelled section transclusion for the citations.

2015-11-03T16:54:17Z

References: Switched to a labelled section transclusion for the citations.

Bugman: Forced creation of a TOC - this will improve the formatting on the main page 'Did you know...' section, and fixes for the sectioning depths.

2015-10-20T18:25:23Z

Forced creation of a TOC - this will improve the formatting on the main page 'Did you know...' section, and fixes for the sectioning depths.

Bugman: /* The Question */ Added Danyun Zeng's email thread.

2015-01-28T09:36:34Z

The Question: Added Danyun Zeng's email thread.

@@ Line 116: / Line 116: @@
 === Recommendation ===
-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]], 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 [https://gna.org/users/semor Sebastien Morin's] consistency testing analysis in relax[Morin and Gagné, 2009] (see http://www.nmr-relax.com/manual/Consistency_testing.html).  That way you can see if your per-experiment temperature calibration and
+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]], 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 {{relax developer link|username=semor|text=Sebastien Morin's}} consistency testing analysis in relax[Morin and Gagné, 2009] (see http://www.nmr-relax.com/manual/Consistency_testing.html).  That way you can see if your per-experiment temperature calibration and
 per-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 R<sub>2</sub> data.

@@ Line 12: / Line 12: @@
 The subject of single field strength data has been discussed numerous times on this mailing list.  It is recommended to read previous responses to questions relating to single field strength data, and look the other messages in those threads.  You will find these discussions quite informative and highly detailed:
-# Danyun Zeng: http://thread.gmane.org/gmane.science.nmr.relax.user/1800
+{| class="wikitable sortable"
-# Sean Leo Moro: http://thread.gmane.org/gmane.science.nmr.relax.user/1787/focus=1788
+|-
-# Martin Ballaschk: http://thread.gmane.org/gmane.science.nmr.relax.user/1409/focus=1438
+! Person
-# Shantanu Bhattacharyya: http://thread.gmane.org/gmane.science.nmr.relax.user/1367/focus=1369
+! Message date
-# Mengjun Xue: http://thread.gmane.org/gmane.science.nmr.relax.user/1276/focus=1277
+! Message ID
-# Fernando Amador: http://article.gmane.org/gmane.science.nmr.relax.user/84
+|-
-# Shantanu Bhattacharyya: http://thread.gmane.org/gmane.science.nmr.relax.user/1086/focus=1087
+| [https://sourceforge.net/p/nmr-relax/mailman/message/36569855/ Danyun Zeng]
-# Dhanasekaran Muthu: http://thread.gmane.org/gmane.science.nmr.relax.user/1152/focus=1153
+| {{#time: Y-m-d H:i:s|Wed, 28 Jan 2015 10:40:23 +0100}}
-# Vitaly Vostrikov: http://thread.gmane.org/gmane.science.nmr.relax.user/1147/focus=1150
+| <small><CAED9pY-m5YEjN6KUX88s_yXLpY1BCudUaVvWWmC0U6WkteDnPA@mail.gmail.com></small>
-# 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
+| [https://sourceforge.net/p/nmr-relax/mailman/message/36569841/ Sean Leo Moro]
-# Keith Constantine: http://thread.gmane.org/gmane.science.nmr.relax.user/513/focus=517
+| {{#time: Y-m-d H:i:s|Fri, 12 Dec 2014 09:24:51 +0100}}
-# Clare-Louise Evans: http://thread.gmane.org/gmane.science.nmr.relax.user/326/focus=332
+| <small><CAED9pY9eAa7B+pC2+RU_pTXWR14fgtiMAiJdQ7rKw+aY6mALaA@mail.gmail.com></small>
-# Hongyan Li: http://thread.gmane.org/gmane.science.nmr.relax.devel/694/focus=701
+|-
 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:

@@ Line 2: / Line 2: @@
 == Reference ==
-http://thread.gmane.org/gmane.science.nmr.relax.user/1552
+https://sourceforge.net/p/nmr-relax/mailman/message/36569608/
 == The Question ==

@@ Line 63: / Line 63: @@
 I must warn you about using single field strength data.  It is now quite difficult to publish a model-free analysis with only single field strength data as most of the field know about the catastrophic analysis failures resulting in large amounts of artificial motion.  These failures can also be much more subtle.  Many reviewers will ask for such data to be collected as the results cannot not be trusted otherwise.  For a model-free analysis, it is almost
-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 R<sub>ex</sub> motions of the [Tjandra et al., 1995] paper.
+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<sub>ex</sub>]] motions of the [Tjandra et al., 1995] paper.
 === Recommendation ===

@@ Line 44: / Line 44: @@
 In summary:
-# 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 for an example of the catastrophic failure that this initial estimate can result in.  Or the bacteriorhodopsin fragment of [Orekhov et al., 1999] where this complete failure was earlier demonstrated.
+<ol style="list-style-type:lower-alpha">
-# 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.  Only relax and [[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>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 for an example of the catastrophic failure that this initial estimate can result in.  Or the bacteriorhodopsin fragment of [Orekhov et al., 1999] where this complete failure was earlier demonstrated.</li>
-# Eliminate failed models (this is only available in relax).  See the [d'Auvergne and Gooley, 2006] model elimination paper.
+  <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.  Only relax and [[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>
-# 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 that paper.
+  <li>Eliminate failed models (this is only available in relax).  See the [d'Auvergne and Gooley, 2006] model elimination paper.</li>
-# Optimise the global model. This is the diffusion tensor plus the model-free models for all spin systems.
+  <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 that paper.</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.
+  <li>Optimise the global model. This is the diffusion tensor plus the model-free models for all spin systems.</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.
+  <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.</li>
-# Monte Carlo simulations for error analysis must be performed at the end.
+  <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.</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-only feature (see the [d'Auvergne and Gooley, 2007] model elimination paper).
+  <li>Monte Carlo simulations for error analysis must be performed at the end.</li>
 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 and the [d'Auvergne and Gooley, 2008b] paper is fully implemented in relax, however this required multiple field strength data.

@@ Line 29: / Line 29: @@
 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)
+* [[Modelfree4]] (with or without the Fast-Modelfree GUI interface)
 * [[DASHA]]
-* Tensor2 and
+* [[Tensor2]] and
-* DYNAMICS
+* [[DYNAMICS]]
 If you play with the optimisation settings you can even find identical results to within machine precision - relax can mimic these other softwares.
@@ Line 65: / Line 65: @@
 === Recommendation ===
-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, 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 [https://gna.org/users/semor Sebastien Morin's] consistency testing analysis in relax[Morin and Gagné, 2009] (see http://www.nmr-relax.com/manual/Consistency_testing.html).  That way you can see if your per-experiment temperature calibration and
+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]], 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 [https://gna.org/users/semor Sebastien Morin's] consistency testing analysis in relax[Morin and Gagné, 2009] (see http://www.nmr-relax.com/manual/Consistency_testing.html).  That way you can see if your per-experiment temperature calibration and
 per-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 R<sub>2</sub> data.

@@ Line 70: / Line 70: @@
 == References ==
-*[*Clore et al., 1990] Clore, G. M., Szabo, A., Bax, A., Kay, L. E., Driscoll, P. C., and Gronenborn, A. M. (1990).  Deviations from the simple 2-parameter model-free approach to the interpretation of N-15 nuclear magnetic-relaxation of proteins. ''J. Am. Chem. Soc.'', '''112'''(12), 4989-4991. (DOI [http://dx.doi.org/10.1021/ja00168a070 10.1021/ja00168a070]).
+*[*Clore et al., 1990] {{#lst:Citations|Clore90}}
-* [*d'Auvergne and Gooley, 2003] d'Auvergne, E. J. and Gooley, P. R. (2003).  The use of model selection in the model-free analysis of protein dynamics. ''J. Biomol. NMR'', '''25'''(1), 25-39. (DOI [http://dx.doi.org/10.1023/a:1021902006114 10.1023/a:1021902006114]).
+* [*d'Auvergne and Gooley, 2003] {{#lst:Citations|dAuvergneGooley03}}
-* [*d'Auvergne and Gooley, 2006] d'Auvergne, E. J. and Gooley, P. R. (2006).  Model-free model elimination: A new step in the model-free dynamic analysis of NMR relaxation data.  ''J. Biomol. NMR'', '''35'''(2), 117-135. (DOI [http://dx.doi.org/10.1007/s10858-006-9007-z 10.1007/s10858-006-9007-z]).
+* [*d'Auvergne and Gooley, 2006] {{#lst:Citations|dAuvergneGooley06}}
-* [*d'Auvergne and Gooley, 2007] d'Auvergne, E. J. and Gooley, P. R. (2007).  Set theory formulation of the model-free problem and the diffusion seeded model-free paradigm.  ''Mol. BioSyst.'', '''3'''(7), 483-494. (DOI: [http://dx.doi.org/10.1039/b702202f 10.1039/b702202f]).
+* [*d'Auvergne and Gooley, 2007] {{#lst:Citations|dAuvergneGooley07}}
-* [*d'Auvergne and Gooley, 2008a] d'Auvergne, E. J. and Gooley, P. R. (2008).   Optimisation of NMR dynamic models I. Minimisation algorithms and their performance within the model-free and Brownian rotational diffusion spaces.  ''J. Biomol. NMR'', '''40'''(2), 107-119. (DOI: [http://dx.doi.org/10.1007/s10858-007-9214-2 10.1007/s10858-007-9214-2]).
+* [*d'Auvergne and Gooley, 2008a] {{#lst:Citations|dAuvergneGooley08a}}
-* [*d'Auvergne and Gooley, 2008b] d'Auvergne, E. J. and Gooley, P. R. (2008).  Optimisation of NMR dynamic models II.  A new methodology for the dual optimisation of the model-free parameters and the Brownian rotational diffusion tensor.  ''J. Biomol. NMR'', '''40'''(2), 121-133. (DOI: [http://dx.doi.org/10.1007/s10858-007-9213-3 10.1007/s10858-007-9213-3]).
+* [*d'Auvergne and Gooley, 2008b] {{#lst:Citations|dAuvergneGooley08b}}
-* [*Morin and Gagné, 2009] Morin, S. and Gagné, S. (2009).  Simple tests for the validation of multiple field spin relaxation data.  ''J. Biomol. NMR'', '''45''', 361-372. (DOI: [http://dx.doi.org/10.1007/s10858-009-9381-4 10.1007/s10858-009-9381-4]).
+* [*Morin and Gagné, 2009] {{#lst:Citations|MorinGagné09}}
-* [*Orekhov et al., 1999] Orekhov, V. Y., Korzhnev, D. M., Diercks, T., Kessler, H., and Arseniev, A. S. (1999). H-1-N-15 NMR dynamic study of an isolated alpha-helical peptide (1-36)bacteriorhodopsin reveals the equilibrium helix-coil transitions. ''J. Biomol. NMR'', '''14'''(4), 345-356. (DOI: [http://dx.doi.org/10.1023/a:1008356809071 10.1023/a:1008356809071]).
+* [*Orekhov et al., 1999] {{#lst:Citations|Orekhov99}}
-* [*Schurr et al., 1994] Schurr, J. M., Babcock, H. P., and Fujimoto, B. S. (1994).  A test of the model-free formulas. Effects of anisotropic rotational diffusion and dimerization. ''J. Magn. Reson. B'', '''105'''(3), 211-224. (DOI: [http://dx.doi.org/10.1006/jmrb.1994.1127 10.1006/jmrb.1994.1127]).
+* [*Schurr et al., 1994] {{#lst:Citations|Schurr94}}
-* [*Tjandra et al., 1995] Tjandra, N., Wingfield, P., Stahl, S., and Bax, A. (1996).  Anisotropic rotational diffusion of perdeuterated HIV protease from N-15 NMR relaxation measurements at two magnetic. ''J. Biomol. NMR'', '''8'''(3), 273-284. (DOI: [http://dx.doi.org/10.1007/bf00410326 10.1007/bf00410326]).
+* [*Tjandra et al., 1995] {{#lst:Citations|Tjandra95}}
 <HarvardReferences />
 == See also ==
 [[Category:Model-free_analysis]]