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CCP4BB  May 2010

CCP4BB May 2010

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Subject:

Re: Micro-g Crystal Growth and the literature

From:

Jan Dohnalek <[log in to unmask]>

Reply-To:

Jan Dohnalek <[log in to unmask]>

Date:

Mon, 10 May 2010 09:17:41 +0200

Content-Type:

text/plain

Parts/Attachments:

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text/plain (131 lines)

Some parameters can be improved BUT the real bottlenecks of the field are in
1. Getting a target soluble at a high concentration.
2. Getting crystals AT ALL.
3. Getting decent diffraction data that then lead hopefully to
structure solution.

No 1 and 2 are the most critical. Space crystallisation does not
overcome either of those.

Jan



On Mon, May 10, 2010 at 5:49 AM, Jack Reynolds <[log in to unmask]> wrote:
> TITLE: "Extracting trends from two decades of microgravity macromolecular crystallization history" (2005) (Judge, Snell and van der Woerd).
>
> "Significant enhancements in structural knowledge have resulted from X-ray diffraction of the crystals grown . . . in the reduced acceleration environnments of an orbiting spacecraft."
>
>
> TITLE: "Macromolecular Crystallization in Microgravity Generated by a Superconducting Magnet" (2006) (Wakayama, Yin, Harata, Kiyoshi, Fujiwara and Tanimoto).
>
> "About 30% of the protein crystals grown in space yield better X-ray diffraction data than the best crystals grown on the earth."
>
>
> TITLE: "The crystallization of biological macromolecules under microgravity: a way to more accurate three-dimensional structures?" (2002) (Lorber).
>
> "The crystallization of proteins . . . in a microgravity environment can produce crystals having lesser defects than crystals prepared under normal gravity on earth. Such microgravity-grown crystals can diffract X-rays to a higher resolution and have a lower mosaic spread."
>
>
> TITLE: "Protein crystal growth on board Shenzhou 3: a concerted effort improves crystal diffraction quality and facilitates structure determination." (2004) (Han, Cang, Zhou, Wang, Bi, Colelesage, Delbaere, Nahoum, Shi, Zhou, Zhue and Lin)
>
> ". . . careful and concerted planning at all stages made it possible to obtain crystals of improved quality compared to their ground controls for some of the proteins. Significantly improved resolutions were obtained from diffracted crystals of 4 proteins. A complete data set from a space crystal of the PEP carboxykinase yielded significantly higher resolution, and a lower average temperature factor than the best ground-based control crystal."
>
>
> TITLE: "JAXA-GCF project - High-quality protein crystals grown under microgravity environment for better understand of protein structure." (2006). (Sato, Tanaka, Inaka, Shinozaki, Yamanaka, Takahashi, Yamanaka, Hirota, Sugiyama, Kato, Saito, Sano, Motohara, Nakamura, Kobayashi, and Yoshitomi.)
>
> "JAXA has developed technologies for growing, in microgravity, high-quality protein crystals, which may diffract up to atomic resolution, for a better understanding of 3-dimensional rpotein structures through X-ray diffraction experiments."
>
>
> TITLE: "A Comparison between Simulations and Experiments for Microgravity Crystal Growth in Gradient Magnetic Fields." (2008). (Poodt, et al.).
>
> "Microgravity protein crystal growth is expected to lead to an improvement of protein crystal quality, compared to crystals grown under normal gravity, due to the suppression of buoyancy driven convection. This is highly relevant, because for protein structure determination by X-ray diffraction, protein crystallization is often the quality limiting step."
>
>
> TITLE: "Macromolecular crystallization in microgravity." (2005) (Snell and Helliwell).
>
> "Density difference fluid flows and sedimentation of growing crystals are greatly reduced when crystallization takes place in a reduced gravity environment."
>
>
> TITLE: "Comparison of space- and ground-grown Bi2Se.21Te2.79 thermoelectric crystals." (2010). (Zhou, et al.)
>
> "The compositions of the space crystal grown along growth direction were more homogeneous than that of the ground crystal grown. The crystallization of space crystal grown was obviously improved."
>
>
> That's just a handful of quotes from a few of the sources I have accumulated over the last few months. I guess this all boils down to your definition of "significantly improved crystals."
>
> Is there something wrong with these sources? Am I misunderstanding their findings?
>
> Jack
>
>
> --- On Sun, 5/9/10, Dunten, Pete W. <[log in to unmask]> wrote:
>
>
>> "significantly improved crystals " I
>> wasn't aware that was an accepted generalization, born out
>> by the experiments already conducted.
>> Can you cite a number of cases?
>>
>> Another issue for pharma would be the timeline.
>> Chemistry programs move pretty fast, and if the xray
>> crystallographers don't keep up,
>> they aren't very useful.
>>
>> Pete
>> ________________________________________
>> From: CCP4 bulletin board [[log in to unmask]]
>> On Behalf Of Jack Reynolds [[log in to unmask]]
>> Sent: Sunday, May 09, 2010 11:26 AM
>> To: [log in to unmask]
>> Subject: [ccp4bb] Clarification and another question . . .
>>
>> --- On Sun, 5/9/10, Klaus Fütterer <[log in to unmask]>
>> wrote:
>>
>> > Dear Jack,
>> >
>> > I believe your venture would enter a mature market,
>> and, if
>> > you were to offer growing growing crystals in
>> microgravity,
>> > a market characterised by very high costs and
>> (presumably)
>> > very low margins.
>>
>> I wouldn't offer crystal growth, I would offer access to
>> the data from x-ray diffraction of space-grown crystals. Is
>> the data from significantly improved crystals not a valuable
>> commodity?
>>
>> If the pharmaceutical industry (and other researchers, for
>> that matter) could grow crystals in space, and extract
>> critical data from the x-ray diffraction of these
>> space-grown crystals (in space); AND
>>
>> if costs could be reduced by 30-50%; AND
>>
>> if the end-product is the data, not the crystals . . .
>>
>> do you still think (profit) margins would be nominal?
>>
>> Is your assessment of "very low margins" based on assumed
>> "very high costs?"
>>
>> Jack
>>
>



-- 
Jan Dohnalek, Ph.D
Institute of Macromolecular Chemistry
Academy of Sciences of the Czech Republic
Heyrovskeho nam. 2
16206 Praha 6
Czech Republic

Tel: +420 296 809 390
Fax: +420 296 809 410

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