Actually, in our hands, we have gotten a mixture of clear drops and
precipitate when scaling from teeny drops to larger ones. Teeny drops
equilibrate faster, and have more pronounced surface and edge effects
than larger ones. We have also found that it is easier to crystallize
salt in teeny drops (and harder to scale salt crystals up).

 

 One of our usual tricks is to dilute the precipitant relative to the
reservoir (2 protein + [1-1.5 precipitant + 0.5-1 water]) , so that as
vapor diffusion progresses, the protein concentrates even more. On
scale-up, we test all permutations of this.

 

It's obvious but maddening: for proteins that are moderately easy to
crystallize (5-10% crystalline hits), it is very easy to translate hits
from teeny scale to large scale. The crystal quality may not be good,
but there will be crystals to test. When there is less than 1% hit rate,
it gets harder. Also, crystals that arise from the muck of the
precipitate are very hard to translate (and repeat). 

 

However,  these are to be preferred to the protein that crystallizes in
>40% of the experiments (but gives uniformly low quality crystals). I
hate it when we have to chase down more than 15 widely different
conditions.

 

Lisa

BTW "teeny" is the highly technical term for drops smaller than 50nl
total volume.

--

Lisa A. Nagy, Ph.D.

University of Alabama-Birmingham

[EMAIL PROTECTED]

 

From: CCP4 bulletin board [mailto:[EMAIL PROTECTED] On Behalf Of
Oganesyan, Vaheh
Sent: Thursday, January 17, 2008 8:41 AM
To: [email protected]
Subject: Re: [ccp4bb] crystallisation robot

 

Mark,

 

What was the state of the larger drops when tiny counterparts had
crystals? My guess - they all precipitated.

I'm trying to understand why some proteins or some conditions require
change in protein concentration while others do not when migrating from
smaller drops to larger ones. If it is protein dependent then I'm afraid
there might be no one answer; if it is not then there should be a trend
and explanation of phenomena.

 

 

Vaheh 

 

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