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 > Gordon & Dorothy Kline Professor > Department of Chemistry > Colgate University > 13 Oak Drive > Hamilton, NY 13346 > > tel: (315)-228-7245 > ofc: (315)-228-7395 > fax: (315)-228-7935 > email: [email protected] > > On 2/10/2012 3:34 PM, Nat Echols wrote: >> On Fri, Feb 10, 2012 at 12:29 PM, James Stroud <[email protected]> >> 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 >>
