Dear Deepak,

As some will have already said a good first check is to X-ray the crystals at 
the temperature they were grown at. This is not too hard and there are numerous 
approaches available. Some synchrotron sources, e.g. SSRL, have even enabled 
this as a remote capability. This can tell you if the initial crystal quality 
is poor or if your cryoprotectant conditions are damaging the initial crystal. 
If they are, there are various approaches to introduce cryoprotectants slowly 
or even increase the cryoprotectant conditions in the initial screen slightly. 
If you plan to use glycerol I would use a small % in the initial solution. You 
do seem to have crystalline ice from your diffraction images.

A very successful and easily implemented approach is seeding. There is quite a 
bit of literature out there and commercial low-cost kits like the seed bead at 
Hampton-Research that can help this. Our Structural Biology Resources page at 
https://hwi.buffalo.edu/structural-biology-resources/ has links to papers in 
this area under the Crystallization Resources section. There may be other 
advice there also.

In our Crystallization Center (http://getacrystal.org) we would typically 
optimize several chemically distinct conditions if multiple initial crystal 
hits were seen. It’s always better to do that rather than focus on a single 
condition.

As others have said, a microfocus source and rastering over the needle-like 
crystals you have may produce some results. More complex, but also seen to be 
successful in cases, is altering the humidity of the crystals. There are 
commercial devices to do this and beamlines equipped with humidity control. 
This is a more technically challenging approach.

Good luck,

Eddie


Edward Snell Ph.D.

President and CEO | Hauptman-Woodward Medical Research Institute
Director | NSF BioXFEL Science and Technology Center
Professor, Materials Design and Innovation | University at Buffalo, SUNY

p: +1 716 898 8631 | f: +1 716 898 8660
e: [email protected]<mailto:[email protected]>
skype: eddie.snell

Hauptman-Woodward Medical Research Institute
700 Ellicott Street | Buffalo, NY 14203-1102
hwi.buffalo.edu<https://hwi.buffalo.edu/>


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From: CCP4 bulletin board <[email protected]> On Behalf Of Deepak Deepak
Sent: Tuesday, May 18, 2021 6:08 AM
To: [email protected]
Subject: [ccp4bb] sugestions on weak diffracting protein crystals

Dear all, I have got multiple crystals (see picture 1) of a protein (8kDa) with 
a helical aromatic oligoamide foldamer (5kDa) but these crystals diffract very 
poorly (see the diffraction&nbs
Caution! This message was sent from outside your organization.

sophospsmartbannerend
Dear all,

I have got multiple crystals (see picture 1) of a protein (8kDa) with a helical 
aromatic oligoamide foldamer (5kDa) but these crystals diffract very poorly 
(see the diffraction pattern in picture 2).

I prepare a 1.3mM:1.3mM complex of protein: foldamer in 20mM Tris, pH 7.5 
buffer. Crystals grew in 3-5 days in sitting and hanging drop at 20 Deg C and 
25 Deg C in the following conditions:

- 20% PEG 400, 0.1M MES pH 6.0
-20% PEG 400, 0.1M Sodium Cacodylate pH 6.0

Multiple cryo used were:
-25%Glycerol in mother solution
 -30% glycerol in water
-30%PEG 400,
-35% PEG 400
-20% PEG 8000 + 40% PEG 400 mix

Kindly suggest some methods/modifications on how can I improve the resolution 
and get better-diffracting crystals. Please let me know if you need more 
information.

Kind regards,
Deepak
Ph.D. Student

PS: The protein is a DNA binding protein and I have crystallized and solved the 
structure of this protein with its DNA partner and now I crystallized it with 
our foldamers but diffraction is not good. There are multiple structures of the 
Protein+DNA complex in literature but no apo-protein structure as the protein 
needs a binding partner to crystallize. We already have solution studies 
showing a good binding.

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