Free R: Difference between revisions

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Eric Martz, Eran Hodis

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-Free R is a statistical quantity introduced in 1992 by Axel T. Brünger<ref>Brünger AT. Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature. 355:472-5. [http://www.ncbi.nlm.nih.gov/pubmed/18481394 PubMed]</ref> to assess the quality of a model from X-ray crystallographic data. It is calculated in the same manner as the R value, but from a subset of the data set aside for the calculation of free R, and not used in the refinement of the model. It is a more reliable tool for assessing the model than the R value because it is not self-referential -- that is, as an estimation of errors, free R is free of any bias that may have been introduced during refinement.
+[[Free R]] (also called R<sub>free</sub>) "is generally considered the most useful global measure of model-to-data agreement"<ref name="validation4pdb">PMID: 22000512</ref>. It is a statistical quantity introduced in 1992 by Axel T. Brünger<ref name="bruenger">PMID: 18481394</ref> to assess the quality of a model from X-ray crystallographic data. It is calculated in the same manner as the [[R value]], but from a subset of the data set aside for the calculation of free R, and not used in the refinement of the model. It is a more reliable tool for assessing the model than the R value because it is not self-referential -- that is, as an estimation of errors, free R is free of any bias that may have been introduced during refinement. Free R is an example of the application of the more general method of [http://en.wikipedia.org/wiki/Cross-validation_(statistics) cross validation].
-As a rule of thumb, free R should not exceed the R value by more than 0.05; that is, if the R value is 0.20, free R should not significantly exceed 0.25. Free R values exceeding 0.40 raise serious doubts about the model.
+==Help Interpreting Free R==
+When a crystallographic protein structure is visualized in [[FirstGlance/Index|FirstGlance in Jmol]], its Free R will be automatically interpreted as ''Reliability'' with the following levels, each relative to its [[Resolution]]:
+*<span style="color:#00e000;font-weight:bold;">Much better than average</span>
+*<span style="color:green;font-weight:bold;">Better than average</span>
+*<span style="color:black;font-weight:bold;">Average</span>
+*<span style="color:#a0a000;font-weight:bold;">Worse than average</span>
+*<span style="color:red;font-weight:bold;">Unreliable</span>
+==Good Values for Free R==
+As a rule of thumb, for models with [[resolution]] of 2.0 &Aring; or better (&Aring; values <2.0), free R should not exceed (resolution/10) by more than 0.05; that is, if the resolution is 2.0 &Aring;, free R should not significantly exceed 0.25. For resolutions around 3.0 &Aring;, the free R should not exceed (resolution/10). Free R values exceeding the worst 25% for the resolution of the model (see table below) raise doubts about the quality of the model.
+Free R is positively correlated with [[resolution]]<ref name="validation4pdb" />:
+:{| cellpadding="4" style="text-align: center; border: 1px solid darkgray;"
+|- style="background: #e0e0e0;"
+! Resolution, &Aring;
+! Median Free R<ref name="validation4pdb" />
+! Median Free R<br>- (Resolution/10)
+! Free R<br>Best 25%
+! Free R<br>Worst 25%
+|-
+| 1.0
+| 0.15
+| 0.05
+| <0.14
+| >0.17
+|-
+| 1.5
+| 0.21
+| 0.06
+| <0.19
+| >0.23
+|-
+| 1.8
+| 0.23
+| 0.05
+| <0.21
+| >0.245
+|-
+| 2.0
+| 0.24
+| 0.04
+| <0.22
+| >0.26
+|-
+| 2.2
+| 0.25
+| 0.03
+| <0.23
+| >0.265
+|-
+| 2.5
+| 0.26
+| 0.01
+| <0.245
+| >0.28
+|-
+| 3.0
+| 0.28
+| <font color="red">- 0.02</font>
+| <0.26
+| >0.30
+|-
+| 3.5
+| 0.30
+| <font color="red">- 0.05</font>
+| <0.275
+| >0.33
+|-
+| ~4.0
+| 0.31
+| <font color="red">- 0.09</font>
+| <0.28
+| >0.35
+|}
+:*Data in the above table for resolutions <= 3.5 &Aring; are approximated from Figure 3C in <ref name="validation4pdb" />, based on X-ray entries deposited in the [[PDB]] since 1990.
+:*Data for resolution ~4.0 &Aring; are based on 199 X-ray entries, for which free R values are given, with resolutions of 3.9-4.1 &Aring; (Feb 2013).
+:*The median resolution for X-ray entries in the [[PDB]] is 2.07 &Aring; (Feb 2013).
+==Bad Values for Free R==
+<!--In October, 2011, there are 79 X-ray crystallographic entries in the [[PDB]] deposited 1990 or later, with free R values of >= 0.40. The median resolution of these 79 entries is 4.2 &Aring;.-->
+In October, 2011, there are 182 X-ray crystallographic entries in the [[PDB]] with free R values of >= 0.37. 45 of these have a resolution <= 3.0 &Aring;, and 5 have a resolution of <= 2.0 &Aring;. It seems likely that there are serious errors in most of these 45 models.
+In one amazing case, [[1zff]], the resolution is given as 0.94 &Aring;, the R value as 0.428, and the free R as 0.444.
+==No Value for Free R==
+In October, 2011, there are 5,908 X-ray crystallographic entries in the PDB for which no free R value is given. These represent 8.8% of all 66,847 X-ray entries. Most of these were deposited before  the free R methodology was described by Brünger in 1992<ref name="bruenger" />.
+:{| cellpadding="4" style="text-align: center; border: 1px solid darkgray;"
+|- style="background: #e0e0e0;"
+! Deposition Date
+! X-ray entries
+! No Free R
+|-
+| Through 1990
+| 666
+| 666 (100%)
+|-
+| 1991-1995
+| 3,209
+| 2,852 (89%)
+|-
+| 1996-2000
+| 8,832
+| 1,858 (21%)
+|-
+| 2001-2005
+| 18,522
+| 342 (1.8%)
+|-
+| 2006-<br>Oct 2011
+| 35,618
+| 190 (0.5%)
+|}
 ==See Also==