Dear Andrew,

did you remove all cysteins, and all methionines with the mutations? Your 
resolution is about 2A, if I understand correctly. This may be suitable for S-
SAD. I would try to get access to a modern inhouse machine to get high quality 
data at high multiplicity. Some modern synchrotron beamlines offer more than 
1-circle goniometers, but good quality data is more easily collected with a 
multi-circle instrument.

Best,
Tim

On Monday, December 19, 2016 4:42:00 PM CET Andrew Lovering wrote:
> Thanks again Herman,
> 
> The protein is a two domain protein (approx 40aa, 350aa split) - searching
> with either is proving fruitless.
> 
> Original, wild-type cell = 49 x 75 x 80 P212121
> This painful mutant = 39 x 157 x 75 beta=98.26 P21
> 
> (so one can say that there seems to be a relationship there, wt b = mutant
> c, wt c = 2x mutant a?)
> 
> We have been bitten in the past by crystallizing contaminants, but (touch
> wood) those are always small crystals one / drop, in a few conditions. This
> problem set has been replicated across at least 6 differing crystals (grown
> in different conditions), where there are many crystals / drop......along
> with the similar cell I'm confident that we are seeing diffraction from
> what we expect
> 
> I will check the diffraction images more closely, but (does anyone agree
> here?) I find this sometimes obscured by modern fine-slice/Pilatus
> methodology
> 
> Might be one for 2017! p.s. no anomalous signal in there - ironically mutant
> we're using knocks bound metal out!
> 
> Thanks again
> Andy
> From: [email protected] [mailto:[email protected]]
> Sent: 19 December 2016 16:26
> To: Andrew Lovering; [email protected]
> Subject: AW: unusual monoclinic relation?
> 
> Dear Andy,
> 
> I don't think you will solve this pre-Xmas, but here are some more
> suggestions: -is there any relationship with the unit cell of the parent,
> unmutated protein? This might give some ideas of the packing of the problem
> crystals. -are some promising solutions being rejected due to clashes? In
> that case you might try to allow for more clashes. -can the protein be
> split in some separate domains? In that case you could try MR with the
> separate domains. -Are you sure the crystallized protein is the protein you
> think you crystallized? (see contamination database). -Check your
> diffraction images to make sure there are no pathologies present.
> 
> Best,
> Herman
> 
> 
> Von: Andrew Lovering [mailto:[email protected]]
> Gesendet: Montag, 19. Dezember 2016 12:30
> An: Schreuder, Herman R&D/DE;
> [email protected]<mailto:[email protected]> Betreff: RE: unusual
> monoclinic relation?
> 
> Thanks Herman. In short:
> 
> -no twinning suggested from xtriage etc
> -P2 doesn't give a solution either
> -monoclinic cell would have 2 (60% solvent) or 3 (40% solvent) copies
> -I originally thought the zanuda P1 route would be the way to go, but phaser
> was still churning away after running overnight and so I killed the job
> thinking it was thrashing
> 
> Andy
> 
> From: [email protected]<mailto:[email protected]>
> [mailto:[email protected]] Sent: 19 December 2016 10:43
> To: Andrew Lovering; [email protected]<mailto:[email protected]>
> Subject: AW: unusual monoclinic relation?
> 
> Dear Andrew,
> 
> Just a few questions:
> -Do the processing/refinement programs suggest twinning?
> -Are you sure your space group is P21 and not P2? Did you try MR in P2?
> -How many protein molecules do you expect in the asymmetric unit?
> 
> P2(1) is a very low symmetry space group. In this case I would not try to be
> clever and just reprocess the data in P1 and run MR in P1. With Zanuda you
> can afterwards try to figure out what the real space group could be.
> 
> Best,
> Herman
> 
> 
> Von: CCP4 bulletin board [mailto:[email protected]] Im Auftrag von
> Andrew Lovering Gesendet: Montag, 19. Dezember 2016 09:43
> An: [email protected]<mailto:[email protected]>
> Betreff: [ccp4bb] unusual monoclinic relation?
> 
> Dear All,
> 
> I have just collected data on a mutant of a protein that should be facile to
> solve by molrep (one residue/320 changed, approx 2Ang resolution) but is
> proving problematic. Data merging stats look good.
> 
> The spacegroup is monoclinic, P21, the cell:
> 
> a=39.47 b=157.36 c=74.9 beta=98.26
> 
> I spotted the relevant monoclinic twin laws on ccp4 twinning page and all
> relate multiples of axes a and c with one another (na +nc etc) but in the
> above case it would appear b~ = 4a
> 
> There are other datasets, all index in this way, some hint at issues by
> indexing with the alternate a=74 b=157 c=79 (where a and c "swap" with a
> doubled, and thus our b=4a turns into b=2c)
> 
> I would appreciate any advice on how to progress! Be nice to solve it
> pre-xmas.....
> 
> Best & thanks in advance,
> Andy

-- 
--
Paul Scherrer Institut
Tim Gruene
- persoenlich -
OFLC/102
CH-5232 Villigen PSI
phone: +41 (0)56 310 5297

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