Hi Natalia,

One rule of thumb in crystallography: anything is possible!

We have seen many cases of individual proteins (or their complexes with small 
molecules, proteins or nucleic acids) where we ended up with structures 
starting from low resolution initial crystals. So before taking a decision, I 
would suggest considering the following:

a) How many of these crystals did you screen? If only a very few, you should 
try more.
b) How big are the crystals?
c) Are these diffraction results from home source or synchrotron?
d) Long long were crystals allowed to grow before you harvested?
e) Did you try a few different cryos to verify they don't show any difference 
despite no visible deterioration?
f) How long does it take to harvest and place in cryo? How long are you soaking 
in cryo before freezing?
g) Are there issues in crystals being stuck in the well or cover slide and you 
have to apply force to dislodge?
h) Are you doing single step cryo or multi-step in increasing amounts of cryo?
i) Did you try growing crystals at different temp (4C and 20C?) or growing with 
cryo?
j) Do you know what the construct of this apo protein can diffract to?

If you have tried all the above, you can then consider trying different DNA 
lengths and blunt-end vs overhangs or different protein constructs.

Happy to discuss more about the specific case.

Best,
Debanu 
Accelero Biostructures 


> On Fri, Mar 2, 2018 at 5:34 PM, Natalia O <natalie.c...@gmail.com> wrote:
> Hello,
> 
> 
> 
> I got crystals of protein-nucleic acid complex, rod-shape, reproducible,
> don’t visibly get damaged upon freezing; however they gave diffraction only
> to about 12 A. I tried several crystals. My question is whether such
> crystals worth optimization. Clearly a 4A diffracting crystal could
> potentially be optimized to 3 – 2.5A, but if the diffraction that I am
> getting now is 12A it could suggest that the system is so flexible that
> getting to 3A with this crystal form is not possible at all. I just wonder
> if there is any statistics or a rule of thumb about what initial diffraction
> worth optimization?
> 
> 
> Thank you!
> 
> -Natalia
> 
> 

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