1.1  Getting many diverse conformations routinely into well-diffracting 
crystals;  and knowing how to interpret them biologically.

On 15/07/2019 20:44, Holton, James M wrote:
> 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 and "winners", to be established along with other unpublished results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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