We have used this work a lot over the years in PDB-REDO and while the model for 
the Rfree/R ratio does not seem to work anymore for model refinement tools, the 
model for sigmaRfree (equal to R-free divided by the square root of the number 
of test set reflections) still holds. Also if you do k-fold cross validation 
(which we do for small test sets) the standard deviation of R-free ends up 
pretty much the same as the predicted value.  

Tim Gruene did work on Rcomplete 
(https://www.pnas.org/doi/10.1073/pnas.1502136112) which combine the results 
form the k refinements in cross validation and Rcomplete comes out to be very 
close to the average Rfree from all k refinements.

In CCP4, k-fold cross validation is easy because your reflections are divided 
in (roughly) equal groups. You just need to set the test set number from 0 to 
all the other values.

Cheers,
Robbie

  

> -----Original Message-----
> From: CCP4 bulletin board <[email protected]> On Behalf Of Gerard
> Bricogne
> Sent: Monday, June 23, 2025 17:38
> To: [email protected]
> Subject: Re: [ccp4bb] free R in shells
> 
> Dear Randy,
> 
>      Might it be these?
> 
>  https://doi.org/10.1107/S0907444997013875
> 
>  https://doi.org/10.1107/S0907444999016868
> 
> 
>      Best wishes,
> 
>         Gerard
> 
> --
> On Mon, Jun 23, 2025 at 03:33:36PM +0000, Randy John Read wrote:
> > Hi,
> >
> > I think it was Ian Tickle who worked out the statistical error in R-free 
> > that
> arises from taking different random samples, though I can’t track down the
> publication quickly. Anyway, the take-home from this is that you don’t expect
> all free sets to give the same R-free, and you shouldn’t over-interpret small
> differences in R-free.
> >
> > Does anyone have the citation for this?
> >
> > Best wishes,
> >
> > Randy
> >
> > > On 23 Jun 2025, at 15:55, Oganesyan, Vaheh
> <[email protected]> wrote:
> > >
> > > <!-- /* Font Definitions */ @font-face {font-family:"Cambria Math";
> > > panose-1:2 4 5 3 5 4 6 3 2 4;} @font-face {font-family:Calibri; panose-1:2
> 15 5 2 2 2 4 3 2 4;} @font-face {font-family:Aptos;} /* Style Definitions */
> p.MsoNormal, li.MsoNormal, div.MsoNormal {margin:0in; font-size:12.0pt;
> font-family:"Aptos",sans-serif;} a:link, span.MsoHyperlink {mso-style-
> priority:99; color:blue; text-decoration:underline;} span.EmailStyle19 {mso-
> style-type:personal-reply; font-family:"Aptos",sans-serif; color:windowtext;}
> .MsoChpDefault {mso-style-type:export-only; font-size:10.0pt; mso-
> ligatures:none;} @page WordSection1 {size:8.5in 11.0in; margin:1.0in 1.0in
> 1.0in 1.0in;} div.WordSection1 {page:WordSection1;} --> Hi all,  I’ve spent
> some time going through different flags for free reflections for (somewhat
> stupid) reason to get lower Rfree. I made sure all different flags were used
> only for each of sets of refinement. I wanted to satisfy my inner belief that 
> it
> doesn’t matter which flag is used (between 0 and 19). To be short: I failed.
> > >  Free reflections have been chosen “randomly”, no suspicion there.
> However, there was clear difference at the end. The difference was about 2-
> 3% difference in Rfree value. This tells me that the randomness has some
> sort of rule, which makes “random” choice not so random. Having found this
> I also tried to see “a rule” that breaks this randomness, like even numbers,
> odds, etc. I did not. Because this was only on few cases I won’t even try to
> connect it to # of molecules per AU, or SG. For each structure (I tried this 
> for
> 2-3 structures about 10 years ago) it was a different flag.
> > > I’m not sure if DCC also is looking through different flags, but at the 
> > > end it
> finds the best, making these exercises unnecessary.
> > > Sorry, cannot present a case. Was too long ago.
> > >  Vaheh Oganesyan, Ph.D.<image001.png>R&D | Biologics Engineering One
> > > Medimmune Way, Gaithersburg, MD 20878
> > > T:  301-398-5851
> > > [email protected]
> > >     From: CCP4 bulletin board <[email protected]> On Behalf Of
> > > Randy John Read
> > > Sent: Monday, June 23, 2025 10:29 AM
> > > To: [email protected]
> > > Subject: Re: [ccp4bb] free R in shells  Hi Ben,
> > >
> > > I would be very interested if you have a case where it makes a difference
> to do this. At one point I was convinced that it had been important when we
> were working on the structure of a Shiga-like toxin bound to trisaccharide
> (1bos), with four pentamers in the asymmetric unit. However, Pavel Afonine
> challenged me to show that the free set was less biased when chosen in
> shells than when chosen randomly, and even in that relatively extreme case I
> couldn’t see evidence of it. So it’s probably not worth the bother. Also, if 
> you
> select the free set randomly, it’s distributed over the same resolutions as 
> the
> working data, which arguably is important when you’re using it to calibrate
> the sigma(A) estimates for likelihood targets.
> > >
> > > Best wishes,
> > >
> > > Randy
> > >
> > > > On 23 Jun 2025, at 12:35, Ben Bax <[email protected]> wrote:
> > > >
> > > > Hi,
> > > > How do you select R-free in shells with CCP4?
> > > > Thanks, Ben Bax
> > > >
> > > >
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> > > Randy J. Read
> > > Department of Haematology, University of Cambridge Cambridge
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> > >
> > >
> > >
> > >
> > >
> > >
> > >
> > >
> >
> > -----
> > Randy J. Read
> > Department of Haematology, University of Cambridge
> > Cambridge Institute for Medical Research     Tel: +44 1223 336500
> > The Keith Peters Building
> > Hills Road                                                       E-mail: 
> > [email protected]
> > Cambridge CB2 0XY, U.K.                              
> > www-structmed.cimr.cam.ac.uk
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