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:[log in to unmask]] On Behalf Of Gerard Bricogne
Sent: Sunday, June 04, 2017 12:07 PM
To: [log in to unmask]
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 <[log in to unmask]> 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
> > >
> > >
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