Well - I didnt want to give Dale a swelled head! But Gerard and Jacob are both right.. E
On 4 June 2017 at 17:51, Keller, Jacob <[email protected]> wrote: > I would resolve this disagreement by repeating that "common sense is not > so common." When I have seen a great scientist, or anyone with wisdom for > that matter, I have seen the ability to demonstrate how complicated > questions can be unravelled in a dazzlingly simple way, such that it almost > seems trivial or common-sensical. Examples would include Richard Feynmann, > the US Supreme Court Justices, and others. I would propose that Eleanor > meant this kind of uncommon common sense. > > JPK > > -----Original Message----- > From: CCP4 bulletin board [mailto:[email protected]] On Behalf Of > Gerard Bricogne > Sent: Sunday, June 04, 2017 12:07 PM > To: [email protected] > Subject: Re: [ccp4bb] Refining a crystal structure with (very) high > solvent content > > Dear Eleanor, > > I think this is too faint a praise for Dale. What he shows in his > reply is not just common sense, but knowledge and understanding of the > fundamentals. You can't do good science with common sense alone, and in our > field common sense will not be of much help if you do not understand the > Fourier transform well enough, for example. > > I would venture to guess that 95+% of crystallographers are in the > unquestioned habit of making the same conceptual error that Dale has > pointed out, viz. mistaking the rmsd of the map (which is a unit of > contrast) for the standard deviation of a noise level in the map. > The latter quantity has nothing to do with the former, as has been pointed > out many times. > > The problem is that this confusion is enshrined in the default values > of certain parameters in display programs and scripts, that are assumed > (not by their authors, but by almost everybody else) to embody all the > common sense we need :-) . > > > With best wishes, > > Gerard. > > -- > On Sun, Jun 04, 2017 at 03:36:29PM +0100, Eleanor Dodson wrote: > > Thank you Dale! You talk so much common sense.. > > Eleanor > > > > On 2 June 2017 at 23:30, Dale Tronrud <[email protected]> wrote: > > > > > On 6/2/2017 1:42 PM, wtempel wrote: > > > > Hello all, > > > > crystals with high solvent content tend to diffract poorly, at > > > > least according to intuition. Several years ago we solved a > > > > structure > > > > <http://www.rcsb.org/pdb/explore/explore.do?structureId=2h58> that > > > > appeared to buck that trend with a solvent content of ≈0.8 and > > > > resolution beyond 2 Å, per merging statistics and visibility of > spots on diffraction images. > > > > I would welcome my colleagues’ opinions as to why I might observe > > > > the > > > > following: > > > > > > > > 1. Paired refinement (similar to Fig. 1 in Karplus&Diederichs > > > > <http://doi.org10.1126/science.1218231>) indicates that adding > any > > > > higher resolution data beyond 3.4 Å, the lowest high resolution > > > > cut-off limit I tried, does not improve R-factors at the common > > > > lower resolution cutoff. Yes, diffraction is anisotropic in this > > > > case, but seemingly not to that extent. I hesitate to “throw out” > > > > all data beyond 3.4 Å, or whatever lower resolution cut-off I > > > > might > > > try. > > > > 2. The Fo-Fc map, when countoured at ± 3 rmsd, includes many more > > > > (uninterpretable) features than I would expect after refinement > to > > > > residuals in the mid-to-lower twenties. For expected map > appearance, > > > > I had to crank up the coutour level to > 5 rmsd, like in the > > > > attached screenshot of the ADP·Mg^++ omit map. > > > > > > This is one of the prime examples of the failure of describing > > > contour levels in terms of "sigma". First, the number you are using > > > is not a "standard deviation" or any other measure of the error > > > level of the map but is simply the rms value of the map. If you > > > calculate the rms of a difference map where 80% of the unit cell is > > > bulk solvent, and therefore flat, you will, of course, get a much > > > smaller number than if the unit cell contained 80% protein with all > > > the the expected difference map features that come from a model with > > > an R value of ~20%. Then when you contour at three times this > > > absurdly small number you will see all sorts of features you are not > > > used to seeing. Selecting a contour level based on the e/A^3 is > > > much less sensitive to the amount of solvent in the crystal is gives > much more consistent results. > > > > > > Dale Tronrud > > > > > > > > Could these observations be linked to the high solvent content? > > > > (1) A high solvent content structure has a higher-than-average > > > > observation-to-parameter ratio, sufficiently high even when > > > > limited to stronger, low-resolution reflections? (2) Map > > > > normalization may not be attuned to such high solvent content? > > > > I am interested in analyzing the automated decision-making of the > > > > PDB-REDO of this entry <http://www.cmbi.ru.nl/pdb_redo/h5/2h58>, > > > > such as paired refinement results and selection of ADP model. > > > > Should I find this information in the “All files (compressed)” > > > > archive > > > > <http://www.cmbi.ru.nl/pdb_redo/cgi-bin/zipper.pl?id=2h58>? The > “fully optimized structure’ > > > > <http://www.cmbi.ru.nl/pdb_redo/h5/2h58/2h58_final.pdb> shows > > > > |ANISOU| cards and |NUMBER OF TLS GROUPS : NULL|. Does this mean > > > > that individual ADPs have been refined anisotropically? > > > > Looking forward to your insights, > > > > Wolfram Tempel > > > > > > > > >
