Dear Frank,
I was going to reply to Ian's last comment last night, but got
distracted.
This last paragraph of Ian's message does sound rather negative
if detached from the context of the previous one, which was about
non-isomorphism between fragment complexes and the apo being the rule
rather than the exception. Ian uses the Crick-Magdoff definition of
an acceptable level of non-isomorphism, which is quite a stringent one
because its refers to a level that would invalidate isomorphism for
experimental phasing purposes. A much greater level of non-isomorphism
can be tolerated when it comes to solving a target-fragment complex
starting from the apo structure, so the Crick-Magdoff criterion is not
relevant here.
Furthermore I think that Ian identifies perhaps too readily the
effect of non-isomorphism in creating "noise" in the comparison of
intensities and its effect on invalidating the working vs. free status
of observations. I think, therefore, that Ian's claim that failing the
Crick-Magdoff criterion for isomorphism results in scrambling the
distinction between the working set and the free set is a very big
overstatement.
You describe as "bookkeeping faff" the procedures that Ian and I
outlined to preserve the FreeR flags of the apo refinement, and ask
for a paper. These matters are probably not glamorous enough to find
their way into papers, and would best be discussed (or re-discussed)
in a specialised BB like this one. If the shift from the question "How
many is too many" to "How the free set should be chosen" that I tried
to bring about yesterday results in a general sharing of evidence that
otherwise gets set aside, I will be very happy. I would find it unwise
to dismiss this question by expecting that there would be a mountain
of published evidence if it was really important.
Let us go ahead, then: could everyone who has evidence (rather
than preconceptions) on this matter please come forward and share it?
Answering this question is very important, even if the conclusion is
that the "faff" is unimportant.
With best wishes,
Gerard.
--
On Thu, Jun 04, 2015 at 10:43:15PM +0100, Frank von Delft wrote:
> I'm afraid Gerard an Ian between them have left me a bit confused
> with conflicting statements:
>
>
> On 04/06/2015 15:29, Gerard Bricogne wrote:
> ><snip>
> >In order to guard the detection of putative bound fragments against the
> >evils of model bias, it is very important to ensure that the refinement of
> >each complex against data collected on it does not treat as free any
> >reflections that were part of the working set in the refinement of the apo
> >structure.
> ><snip>
>
> On 04/06/2015 17:34, Ian Tickle wrote:
> ><snip>
> >So I suspect that most of our efforts in maintaining common free R
> >flags are for nothing; however it saves arguments with referees
> >when it comes to publication!
> ><snip>
>
>
> I also remember conversations and even BB threads that made me
> conclude that it did NOT matter to have the same Rfree set for
> independent datasets (e.g. different crystals). I confess I don't
> remember the arguments, only the relief at not having to bother with
> all the bookkeeping faff Gerard outlines and Ian describes.
>
> So: could someone explain in detail why this matters (or why not),
> and is there a URL to the evidence (paper or anything else) in
> either direction?
>
> (As far as I remember, the argument went that identical free sets
> were unnecessary even for exactly isomorphous crystals. Something
> like this: model bias is not a big deal when the model has largely
> converged, and that's what you have for molecular substitution (as
> Jim Pflugrath calls it). In addition, even a weakly binding
> fragment compounds produces intensity perturbations large enough to
> make model bias irrelevant.)
>
> phx
