I dont think you expect much better R factors with twinning or without -
the fact is the "crystal"  is not perfect . Sometimes it is worth screening
other crystals from the batch - smaller ones may not be twinned at all..
Have you looked back atthe images? Gerard suggested there might be lattice
translocation..
Eleanor

On Tue, 31 Aug 2021 at 16:46, Peer Mittl <[email protected]> wrote:

> Dear Herman, Kay, Eleanor and CCp4C
>
> At the beginning I was very enthusiastic about the twinning option, but
> meanwhile the enthusiasm has vanished. I basically get the same Rfactors
> after refining the structure in P32 with 5 chains in Refmac (test
> reflections selected in resolution shells with sftools straight from the
> beginning).
>
> Refinement with tight NCS restrains on 4 chains and twinning results in
> Rf/Rfree 24.2/30.0, without twinning I get 27.0/32.5. With slightly relaxed
> NCS restrains for the side chains and no twinning its 24.3/31.8. A Rfree
> difference of 2% is that sufficient to confirm twinning?
>
> What bothers me even more is the difference ED for the "extra" chain (the
> on on the special position in P3221). After refienement with twinning the
> difference density is slightly reduced but it is still present.
> Furthermore, I can replace the "extra" chain by a 180° rotated copy and the
> refinemnt ends up in basically the same Rfactors. I attached two screen
> shots from the superposition of the initial structure (all atoms in wheat)
> on the rotated structure (blue Ca-trace) with the corresponding ED maps.
>
> All the best,
> Peer
>
> -----"CCP4 bulletin board" <[email protected]> schrieb: -----
> An: [email protected]
> Von: "Schreuder, Herman /DE"
> Gesendet von: "CCP4 bulletin board"
> Datum: 27.08.2021 16:37
> Betreff: [ccp4bb] AW: [ccp4bb] AW: [ccp4bb] Antwort: Re: [ccp4bb] chain on
> 2-fold axis?
>
>
>  Dear Lijun and others,
>
>  As Kay rightly pointed out, twinning is fundamentally different from e.g.
> disorder or alternative conformations. However, it does not depend on a
> chain or side chain rapidly jumping  between two states, but whether they
> are within coherent length of each other. Since most data are collected
> from frozen crystals, no side chain will be rapidly jumping between two
> states. They will be frozen either conformation A or conformation B and
> since  these conformations are randomly distributed throughout the crystal,
> they are in general within coherent length of each other and causing
> interference of their diffracted X-ray’s, so their complex structure
> factors are added.
>
>  However, for twinned crystals, the twin domains (twin pieces as you call
> it), behave as independent crystals and their intensities are added and not
> their (complex) structure factors.
>
>  I did not realize it when I first looked at the thread but the correct
> treatment of these crystals will depend on whether there are twin domains
> present in the crystals, or whether the  two orientations of the disordered
> chain are randomly distributed throughout the crystal. Given that the two
> orientations have different twin fractions, my bet is that the twin
> supporters are right.
>
>  Best,
>  Herman
>
>
>
>
>
>  Von: Lijun Liu <[email protected]>
>  Gesendet: Freitag, 27. August 2021 15:57
>  An: Schreuder, Herman /DE <[email protected]>
>  Cc: [email protected]
>  Betreff: Re: [ccp4bb] AW: [ccp4bb] Antwort: Re: [ccp4bb] chain on 2-fold
> axis?
>
>  Dear Herman:
>
>
>
>  if you say “twinned” chains, then it already means same thing of the two
> and the side chain interactions could not be different (as you can see only
> one copy in the output coordinates), unless you talking about borders
> between twin pieces.
>
>
>
>  In this situation, the only I could imagine to be if P3221, it would have
> to make that chain very very rapidly jump between two states in the same
> asu, which can be easily proven wrong.
>
>
>
>  I do agree if refined under P3221 without restraining the two strictly,
> side chain interactions may show differences —— data always not perfect!
>
>
>
>  Lijun
>
>  Sent from my iPhone
>
>
>
>
>   On Aug 27, 2021, at 8:12 AM, Schreuder, Herman /DE <
> [email protected]> wrote:
>
>  
>  Dear Lijun,
>  with this argument I agree: the interactions between the two orientations
> of the “twinned” chain and the neighboring molecules will be different and
> the interacting side chains will  almost certainly have different
> orientations, which necessitates a twinning of the whole structure.
>  Best,
>  Herman
>
>
>
>  Von: CCP4 bulletin board <[email protected]> Im Auftrag von Lijun Liu
>  Gesendet: Freitag, 27. August 2021 14:22
>  An: [email protected]
>  Betreff: Re: [ccp4bb] AW: [ccp4bb] Antwort: Re: [ccp4bb] chain on 2-fold
> axis?
>
>
>  I believe it is a twin from P32.
>
>
>
>
>
>
>
> Not like the assignment of double conformations with partial occupancies
> to small part of asu, for examples, a side chain of lysin or a small
> fragment of a protein, which have both conformations stayed in the same
> specific asu at the same time.  For  this p3221 asu, if one copy of that
> chain occupies the part of the asu, the other so-called conformation will
> not appear in the same asu at the same time, so the conformation and
> occupancy issue was arisen from different cell units, it is a twin from
> p32.
> Talking about the asu of p3221, it holds 3 chains, the chain of interest
> assigned as 2 conformations related by a strict 2-fold.  Since you believe
> and have reduced to P3221,  then you should restrain the two overall
> strictly (since absolutely most of these atoms are not on special
> positions) and not to refine the two 0.5 occupancies either, respecting the
> crystallographic 2-fold.  This  is equivalent to perfect twin from p32
> theoretically (although refinement with twin mode in p32 and none-twin mode
> in p3221 may give difference even large).  If you refined and resulted in
> occupancies away from 0.5, the symmetry was proven to be broken, which
> supports P32 twinning.   Lijun
>
>
>  Sent from my iPhone
>
>
>
>
>
>   On Aug 27, 2021, at 6:56 AM, Oganesyan, Vaheh <
> [email protected]> wrote:
>
>  
>  How P3221 can be an option if it assumes chain on axis? I guess I’m
> missing something, but per my belief only those sg will be possible for
> which there is no axis going through the extra molecule. P1 sg looks the
> only correct option here  in my humble opinion.
>  Democracy (voting) depends on science. However, the reverse is not,
> thankfully.
>
>  Vaheh
>
>
>
>  From: CCP4 bulletin board <[email protected]> On Behalf Of Peer Mittl
>  Sent: Friday, August 27, 2021 6:32 AM
>  To: [email protected]
>  Subject: Re: [ccp4bb] AW: [ccp4bb] Antwort: Re: [ccp4bb] chain on 2-fold
> axis?
>
>  Dear Herman,
>
>  The answer probably depends on the impact of the "extra" chain on the
>  sublattice. If there is no impact the "true" space group is P3221 with
>  one chain on the special position. If the swapping of the extra chain
>  influences the sublattice P32 (or C2 or P1, as pointed out by Kay)
>  twinned to P3221 might be the better description.
>
>  All the best,
>  Peer
>
>  On 27.08.2021 10:56, Schreuder, Herman /DE wrote:
>  >
>  > Dear Peer and Eleanor,
>  >
>  > This is indeed what I am suspecting: If the “twinning operator” in P32
>  > puts 4 out of 5 protein chains on top of symmetry mates, is the “true”
>  > space group then P32, with 5 twinned chains, or P3221 with 4 normal
>  > chains and 1 chain on a special position? I would vote for the latter.
>  >
>  > Best,
>  >
>  > Herman
>  >
>  > *Von:* CCP4 bulletin board <[email protected]> *Im Auftrag von
>  > *Peer Mittl
>  > *Gesendet:* Freitag, 27. August 2021 10:17
>  > *An:* [email protected]
>  > *Betreff:* Re: [ccp4bb] Antwort: Re: [ccp4bb] chain on 2-fold axis?
>  >
>  > Dear Eleanor,
>  >
>  > I indeed used r/tefmac for the refinement and it came up with the values
>  > HKL (a=0.56), KH-L (a=0.44). It would be interesting to see if a
>  > refinement in P3221 would come up with the same occupancies for the
>  > alternative conformations for the "extra" chain on the 2-fold axis. It
>  > seems as if the "well-ordered" chains (2 in P3221, 4 in P32) form a
>  > sublattice with P3221 symmetry and it's just the "extra" chain, which
>  > generates the twinning.
>  >
>  > All the best,
>  > Peer
>  >
>  > On 26.08.2021 18:09, Eleanor Dodson wrote:
>  > > Motto =mitti in predictive text!
>  > >
>  > > On Thu, 26 Aug 2021 at 16:52, Eleanor Dodson
>  > > <[email protected] <mailto:[email protected]
>  > <mailto:[email protected]%20%3cmailto:[email protected]>>>
>
>  > wrote:
>  > >
>  > > Great, motto. I think you have nailed it! Did you use tefmac for
>  > > twinned refinement? And if so what did it suggest the twin
>  > >  fraction is?
>  > >
>  > > On Thu, 26 Aug 2021 at 16:30, Peer Mittl <[email protected]
>  > <mailto:[email protected]%0b>> <mailto:[email protected]
>  > <mailto:[email protected]>>> wrote:
>  > >
>  > > Yes, the data indeed seems to be twinned and the tNCS has
>  > > masked the twinning statistics, which is why I haven't
>  > > considered it so far.
>  > >
>  > > I have not tried twinned refinement in C2 and P1 yet, but
>  > > refining 4 chains in P32 with twinning yields a difference ED
>  > > map that clearly indicates one (and just on!) orientation for
>  > > the 5th chain. Thank you all for your suggestions.
>  > >
>  > > Have a nice evening,
>  > > Peer
>  > >
>  > > -----"CCP4 bulletin board" <[email protected]
>  > <mailto:[email protected]%0b>> <mailto:[email protected]
>  > <mailto:[email protected]>>> schrieb: -----
>  > > An: [email protected] <mailto:[email protected]>
>  > <mailto:[email protected] <mailto:[email protected]>>
>  > > Von: "Kay Diederichs"
>  > > Gesendet von: "CCP4 bulletin board"
>  > > Datum: 26.08.2021 16:41
>  > > Betreff: Re: [ccp4bb] chain on 2-fold axis?
>  > >
>  > > Dear Peer,
>  > >
>  > > I suspect that the true spacegroup has lower symmetry than
>  > > P3221, and that there may be twinning masked by tNCS.
>  > > Subgroups of P3221 are C2 and P32 (
>  > >
>  >
> https://strucbio.biologie.unikonstanz.de/xdswiki/index.php/Space_group_determination#Subgroup_and_supergroup_relations_of_these_space_groups
>  > <
> https://strucbio.biologie.unikonstanz.de/xdswiki/index.php/Space_group_determination#Subgroup_and_supergroup_relations_of_these_space_groups
> >
>  > >
>  > <
> https://strucbio.biologie.unikonstanz.de/xdswiki/index.php/Space_group_determination#Subgroup_and_supergroup_relations_of_these_space_groups
>  > <
> https://strucbio.biologie.unikonstanz.de/xdswiki/index.php/Space_group_determination#Subgroup_and_supergroup_relations_of_these_space_groups
> >>
>  > > )
>  > > and of course P1.
>  > > What I'd do is process the data, and solve (use the best chain
>  > > of the refined P3221 model for MR) and refine the structure in
>  > > these spacegroups.
>  > > Inspect the results: If P1 is clearly better than P32 and C2,
>  > > P1 is correct.
>  > > If C2 (P32) is clearly better than P32 (C2), then P1 should
>  > > give the same R-values as the better one; if so, P1 can be
>  > > discarded.
>  > > Try this with and without twin refinement - although it's hard
>  > > to compare R-values of non-twinned and twinned refinements.
>  > >
>  > > The automatic way to do this is with Zanuda. If you run that
>  > > locally, you can make refmac do twin refinement.
>  > >
>  > > For all resulting structures, I'd also feed the resulting
>  > > Fcalc (!) into pointless. That should reveal that the packing
>  > > is indeed close to P3221.
>  > >
>  > > Best wishes,
>  > > Kay
>  > >
>  > >
>  > > On Thu, 26 Aug 2021 11:54:06 +0200, Peer Mittl
>  > > <[email protected] <mailto:[email protected]
>  > <mailto:[email protected]%20%3cmailto:[email protected]>>> wrote:
>  > >
>  > > >Der CCP4 community,
>  > > >
>  > > >Is there a refinement program that can handle protein
>  > > monomers sitting
>  > > >on crystallographic 2-folds?
>  > > >
>  > > >This is probably a strange question but we have the following
>  > > situation.
>  > > >We have a 2.6 Ang datasets in SG P3221 (Rpim=4%, Isa=19.6)
>  > > and a clear
>  > > >molrep solution with 2 chains, albeit with tNCS (0/0/0.5)
>  > > that can be
>  > > >refined to around 27/33% Rfactor. According to Vm a third
>  > > chain could be
>  > > >present. So far so good, but there is clear difference ED for
>  > > a third
>  > > >chain sitting exactly on the 2-fold. Since the protein has a
>  > > peculiar
>  > > >shape, one can tell even its orientation. I can relax the
>  > > symmetry to
>  > > >P32 (or even P1) and place the missing chain with 50%
>  > > occupancy on the
>  > > >2-fold. This model can be refined, but I do not like this
>  > > work around,
>  > > >because the data is clearly P3221.
>  > > >
>  > > >Any hints on similar crystal pathologies and how they have
>  > > been handled
>  > > >would be helpful.
>  > > >
>  > > >All the best,
>  > > >Peer
>  > > >
>  > >
>  >
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>  > --
>  > ****************************
>  > Peer Mittl, PD Dr.
>  > Biochemisches Institut
>  > Universität Zürich
>  > Room 44M03
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>  >
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