When one finds the 3D structure of a protein by crystalizing it and then making a X-ray experiment, how does one know that the geometrical configuration of the crystal is the same (or even close) to the structure the protein adopt in aqueous solution?

  • $\begingroup$ Well, it doesn't need to be, be it's still something. NMR is getting structures in solutions. $\endgroup$
    – Mithoron
    Commented Mar 31, 2016 at 16:30
  • $\begingroup$ @Mithoron And they're doing fancy stuff with proteins NMR, but I don't see how they would get a whole configuration. That would be amazing. $\endgroup$ Commented Mar 31, 2016 at 17:08
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    $\begingroup$ @DGS Significant percent of protein structures was obtained with NMR not X-ray. rcsb.org/pdb/static.do?p=general_information/about_pdb/… $\endgroup$
    – Mithoron
    Commented Mar 31, 2016 at 17:22
  • $\begingroup$ @Mithoron And to think I have trouble assinging something that weighs around 500 g/mol. $\endgroup$ Commented Mar 31, 2016 at 18:23

1 Answer 1


I'll use quotes from B. Rupp, Biomolecular Crystallography (p. 7-8) to answer.

Generally the structure is similar...

Comparison of many nuclear magnetic resonance (NMR) solution structure ensembles with crystallographic structure has shown that the core structure of protein molecules remains unchanged compared with the solution state during crystallization. In addition, enzymes packed in crystals even maintain biological activity.

with some parts not visible in the experiment...

The maintenance of the core structure and of enzymatic function shows that crystal structures are a very good approximation of the native protein solution structure. Nonetheless, highly flexible or mobile regions, frequently the amino- or carboxyl-termini of the protein chain or flexible loops connecting secondary structure elements, can be poorly defined or even absent in the electron density and thus can be modeled only with limited confidence.

but beware...

In certain situation flexible and dynamic regions of a protein molecule can be rigidly fixed in a specific conformation as a result of crystal packing interactions. In most cases this represents just a snapshot of one possible conformation out of many and it must be understood that such a specific conformation may not locally represent the protein structure in solution. A simple safeguard against misinterpretations -- which is usually assignment of certain biological relevance to regions where that is de facto not warranted -- is to display all neighboring, symmetry-related molecules in the crystal structure and examine if any intermolecular interactions are present that are a result of crystal packing. Such packing induced artifacts can also hamper for example drug discovery by altering or blocking binding sites and thus preventing an otherwise active substance from binding.


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