NMR Ensembles of Models
NMR Experiments Yield Multiple ModelsNMR 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.)
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 ModelsMeaning 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 factor 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.
The Most-Representative ModelThe Most-Representative Model
The most representative model is the model closest to the average model. A server called Olderado reports the most representative model.
The Minimized Average ModelThe 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 does not say).
Median Size of Published NMR StructuresMedian Size of Published NMR Structures
Solution NMR is unable to determine atomic resolution protein structures for molecules in excess of about 30,000 Daltons. In fact, the median mass of NMR structures published in the Protein Data Bank is about 9 kD.
Alignment of ModelsAlignment of Models
NMR models are typically aligned by the authors before publication. However, there are some exceptions.