Excellent question :)

First of all, thank you for putting this out to the community!

Secondly, I agree with several of us who've written that a single
conference is not enough to discuss all the possible topics.

Thirdly, in my opinion all the other problems are secondary to the main
(and only remaining!) problem in crystallography: getting
diffraction-quality protein crystals reproducibly and quickly

The amount of funding for serious crystallization research seems to be
close to non-existent. In general methodology funding is hard to get, but
crystallization seems to me like the absolute underdog of the method pool -
the true 'red headed stepchild' of the methods development funders.

At risk of repeating myself - the other problems (worthy, significant, and
urgent as they are!) are subservient to the main issue at hand - namely
that crystallization remains an unpredictable and artful phenomenon while
literally all other aspects of structure determination process (the gene to
structure pipeline, whatever you might call it)have made astronomic leaps
forward.

Artem
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On Mon, Jul 15, 2019 at 3:44 PM Holton, James M <
0000270165b9f4cf-dmarc-requ...@jiscmail.ac.uk> 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 and "winners", to be established along with other unpublished results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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