Along the lines of Roger's second point, there was a very nice paper a few years back that found very good agreement between the conformational ensemble sampled by ubiquitin in solution (by NMR) with the ensemble of conformations observed in a large number of crystal structures:
Lange OF, Lakomek NA, Farès C, Schröder GF, Walter KF, Becker S, Meiler J, Grubmüller H, Griesinger C, de Groot BL.
Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution.
Science. 2008 Jun 13;320(5882):1471-5. PubMed PMID: 18556554.
Best,
Damian Ekiert
On Feb 10, 2012, at 12:50 PM, Roger Rowlett wrote:
> I believe the most justifiable assumption one can make is that crystal structures are likely to represent the least soluble conformations of a protein under the conditions of crystallization (which might be a broad range of conditions, including physiological). This can be quite vexing if you are studying an allosteric protein and one of the two conformations is typically much less soluble than the other. BTDT. I'm sure others have had the same experience.
>
> Having said that, the solvent content of protein crystals (which is close to that of cellular conditions), the observation of enzymatic activity in many protein crystals, and the *general* concordance of XRD and NMR structures of proteins (when both have been determined) leads one to believe that XRD structures are likely representative of physiologically relevant conformations.
>
> Cheers,
>
> _______________________________________
> Roger S. Rowlett
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> On 2/10/2012 3:34 PM, Nat Echols wrote:
>> On Fri, Feb 10, 2012 at 12:29 PM, James Stroud <[log in to unmask]>
>> wrote:
>>
>>> How could they not be snapshots of conformations adopted in solution?
>>>
>> Packing billions of copies of an irregularly-shaped protein into a
>> compact lattice and freezing it to 100K isn't necessarily
>> representative of "solution", especially when your solution contains
>> non-physiological amounts of salt and various organics (and possibly
>> non-physiological pH too).
>>
>> -Nat
>>
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