Hi James,

2 things come to mind.

1) What are the tools we can use for metals in structural biology? Note, I am 
biased here…

2) Micro electron diffraction methods - ability to use on small crystals (which 
speaks to Tom’s point) and a potential bridge between cryo-EM and X-ray 
diffraction techniques?

Awesome that you are asking for community engagement on this!
Cheers,
Sarah


Sarah EJ Bowman, PhD

Associate Research Scientist, Hauptman-Woodward Medical Research Institute
Director, High-Throughput Crystallization Screening Center

www.getacrystal.org

sbow...@hwi.buffalo.edu

________________________________________
From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of Peat, Tom 
(Manufacturing, Parkville) <tom.p...@csiro.au>
Sent: Monday, July 15, 2019 8:07 PM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: challenges in structural biology

Hello Tim,

I'm not sure this question is specific to crystallography- I believe the same 
can be asked of any experiment in any field?
And if one wants to get into true costs- was it worth it to build the Large 
Hadron Collider to statistically prove that the Higgs boson exists?
I'm guessing it was worth it to the folks that got their name on the paper...
Cheers, tom

-----Original Message-----
From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Tim Grüne
Sent: Tuesday, 16 July 2019 6:09 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] challenges in structural biology

Dear James,

10) are the biological questions that you can answer with a (crystal) structure 
sufficiently relevant to justify the resources?

Best,
Tim



Am 15.07.2019 21:44, schrieb Holton, James M:
> Hello folks,
>
> I have the distinct honor of chairing the next Gordon Research
> Conference on Diffraction Methods in Structural Biology (July 26-31
> 2020).  This meeting will focus on the biggest challenges currently
> faced by structural biologists, and I mean actual real-world
> challenges.  As much as possible, these challenges will take the form
> of friendly competitions with defined parameters, data, a scoring
> system, and "winners", to be established along with other unpublished
> results only at the meeting, as is tradition at GRCs.
>
> But what are the principle challenges in biological structure
> determination today?  I of course have my own ideas, but I feel like
> I'm forgetting something.  Obvious choices are:
> 1) getting crystals to diffract better
> 2) building models into low-resolution maps (after failing at #1)
> 3) telling if a ligand is really there or not
> 4) the phase problem (dealing with weak signal, twinning and
> pseudotranslation)
> 5) what does "resolution" really mean?
> 6) why are macromolecular R factors so much higher than small-molecule
> ones?
> 7) what is the best way to process serial crystallography data?
> 8) how should one deal with non-isomorphism in multi-crystal methods?
> 9) what is the "structure" of something that won't sit still?
>
> What am I missing?  Is industry facing different problems than
> academics?  Are there specific challenges facing electron-based
> techniques?  If so, could the combined strength of all the world's
> methods developers solve them?  I'm interested in hearing the voice of
> this community.  On or off-list is fine.
>
> -James Holton
> MAD Scientist
>
>
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--
--
Tim Gruene
Head of the Centre for X-ray Structure Analysis Faculty of Chemistry University 
of Vienna

Phone: +43-1-4277-70202

GPG Key ID = A46BEE1A

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