NMR Ensembles of Models: Difference between revisions

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The example at right shows the 3 models for [[1lcd]], a lac repressor domain bound to DNA, with one sodium ion. Water is present in this model but for clarity, Proteopedia does not show water in its initial scene.

==NMR Experiments Yield Multiple Models==

==Multiple Model Ensembles from NMR==

===NMR Experiments Yield Multiple Models===

When a macromolecular structure is determined by nuclear magnetic resonance (NMR) in solution, the result is an '''ensemble of multiple molecular models''', each of which is consistent with the experimental data. The results of an NMR experiment are a large number of inter-atomic distance restraints, which are consistent with multiple models. This is in contrast to the result of an X-ray crystallographic experiment, which is a single model that best fits the empirical electron density. (In some cases where the resolution is very high, the model may include alternative positions for some atoms.)

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The number of NMR models published depends upon the experiment and is up to the authors, and varies between 2 and over 100. The first model in the ensemble has no special significance.

==Meaning of the Variation Between Models==

===Meaning of the Variation Between Models===

The '''variation between models''' in the ensemble can mean either of two things. The variation can represent actual '''flexibility and thermal motion''' that occurred during the NMR measurements in solution, typically at room temperature. Alternatively, the variation can simply mean '''uncertainty in the atomic positions''', namely, that an inadequate number of restraints were available to determine the positions of some atoms. Unfortunately, there is nothing comparable to the [[B value]] or [[Temperature value]] that quantitates the uncertainty of the position of each atom in crystallographic results. Hence, the only way to find out what the meaning of the variation between models is to contact the experimenters who authored the published ensemble of models.

Using appropriate methodologies, it is possible to determine both the average structure and its dynamic movements<ref>Simultaneous determination of protein structure and dynamics. Kresten Lindorff-Larsen, Robert B. Best, Mark A. DePristo, Christopher M. Dobson, and Michele Vendruscolo (2005). Nature 433:128. PMID:[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15650731 15650731].</ref>.

===The Most-Representative Model===

The '''most representative model''' is the model closest to the average model. A server called [http://www.ebi.ac.uk/msd-srv/pqs/pqs-nmr.html Olderado] reports the most representative model.

===The Minimized Average Model===

It is common to average the models from an NMR experiment, but in order for the result to be realistic, it must undergo some energy minimization in order to adjust covalent bond lengths and angles. The result is called a '''minimized average model'''. Sometimes, authors publish both the ensemble and the minimized average. For example [[2bbm]] appears to be the minimized average for the ensemble of 21 models in [[2bbn]], but without reading the original publication or contacting the authors, it is difficult to be sure (since the header of the [[PDB file format|PDB file]] does not say).

==Reliability of NMR Models==

NMR models are more likely to contain major errors <ref>Traditional biomolecular structure determination by NMR spectroscopy allows for major errors. Sander B. Nabuurs, Chris. A. E. M. Spronk, Geerten W. Vuister, and Gert Vriend. (2006). PLoS Computational Biology 2: [http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020009 Open Access Full Text] [http://proteinexplorer.org/favlit/nmr.htm Precis]. DOI: 10.1371/journal.pcbi.0020009</ref> than are crystallographic models that have good [[Resolution]] and [[Free R]] values.

~~==The Most-Representative Model==~~

~~The '''most representative model''' is the model closest to the average model. A server called [http://www.ebi.ac.uk/msd-srv/pqs/pqs-nmr.html Olderado] reports the most representative model.~~

~~==The Minimized Average Model==~~

It is common to average the models from an NMR experiment, but in order for the result to be realistic, it must undergo some energy minimization in order to adjust covalent bond lengths and angles. The result is called a '''minimized average model'''. Sometimes, authors publish both the ensemble and the minimized average. For example [[2bbm]] appears to be the minimized average for the ensemble of 21 models in [[2bbn]], but without reading the original publication or contacting the authors, it is difficult to be sure (since the header of the [[PDB file format|PDB file]] does not say).

==Median Size of Published NMR Structures==

NMR Ensembles of Models: Difference between revisions

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@@ Line 19: / Line 19: @@
 The example at right shows the 3 models for [[1lcd]], a lac repressor domain bound to DNA, with one sodium ion. Water is present in this model but for clarity, Proteopedia does not show water in its initial scene.
-==NMR Experiments Yield Multiple Models==
+==Multiple Model Ensembles from NMR==
+===NMR Experiments Yield Multiple Models===
 When a macromolecular structure is determined by nuclear magnetic resonance (NMR) in solution, the result is an '''ensemble of multiple molecular models''', each of which is consistent with the experimental data. The results of an NMR experiment are a large number of inter-atomic distance restraints, which are consistent with multiple models. This is in contrast to the result of an X-ray crystallographic experiment, which is a single model that best fits the empirical electron density. (In some cases where the resolution is very high, the model may include alternative positions for some atoms.)
@@ Line 25: / Line 26: @@
 The number of NMR models published depends upon the experiment and is up to the authors, and varies between 2 and over 100. The first model in the ensemble has no special significance.
-==Meaning of the Variation Between Models==
+===Meaning of the Variation Between Models===
 The '''variation between models''' in the ensemble can mean either of two things. The variation can represent actual '''flexibility and thermal motion''' that occurred during the NMR measurements in solution, typically at room temperature. Alternatively, the variation can simply mean '''uncertainty in the atomic positions''', namely, that an inadequate number of restraints were available to determine the positions of some atoms. Unfortunately, there is nothing comparable to the [[B value]] or [[Temperature value]] that quantitates the uncertainty of the position of each atom in crystallographic results. Hence, the only way to find out what the meaning of the variation between models is to contact the experimenters who authored the published ensemble of models.
 Using appropriate methodologies, it is possible to determine both the average structure and its dynamic movements<ref>Simultaneous determination of protein structure and dynamics. Kresten Lindorff-Larsen, Robert B. Best, Mark A. DePristo, Christopher M. Dobson, and Michele Vendruscolo (2005). Nature 433:128. PMID:[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15650731 15650731].</ref>.
+===The Most-Representative Model===
+The '''most representative model''' is the model closest to the average model. A server called [http://www.ebi.ac.uk/msd-srv/pqs/pqs-nmr.html Olderado] reports the most representative model.
+===The Minimized Average Model===
+It is common to average the models from an NMR experiment, but in order for the result to be realistic, it must undergo some energy minimization in order to adjust covalent bond lengths and angles. The result is called a '''minimized average model'''. Sometimes, authors publish both the ensemble and the minimized average. For example [[2bbm]] appears to be the minimized average for the ensemble of 21 models in [[2bbn]], but without reading the original publication or contacting the authors, it is difficult to be sure (since the header of the [[PDB file format|PDB file]] does not say).
 ==Reliability of NMR Models==
 NMR models are more likely to contain major errors <ref>Traditional biomolecular structure determination by NMR spectroscopy allows for major errors. Sander B. Nabuurs, Chris. A. E. M. Spronk, Geerten W. Vuister, and Gert Vriend. (2006). PLoS Computational Biology 2: [http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020009 Open Access Full Text] [http://proteinexplorer.org/favlit/nmr.htm Precis]. DOI: 10.1371/journal.pcbi.0020009</ref> than are crystallographic models that have good [[Resolution]] and [[Free R]] values.
-==The Most-Representative Model==
-The '''most representative model''' is the model closest to the average model. A server called [http://www.ebi.ac.uk/msd-srv/pqs/pqs-nmr.html Olderado] reports the most representative model.
-==The Minimized Average Model==
-It is common to average the models from an NMR experiment, but in order for the result to be realistic, it must undergo some energy minimization in order to adjust covalent bond lengths and angles. The result is called a '''minimized average model'''. Sometimes, authors publish both the ensemble and the minimized average. For example [[2bbm]] appears to be the minimized average for the ensemble of 21 models in [[2bbn]], but without reading the original publication or contacting the authors, it is difficult to be sure (since the header of the [[PDB file format|PDB file]] does not say).
 ==Median Size of Published NMR Structures==