Dear Kay, Even the small, badly diffracting and 'messed up' crystals are still crystals. There is literally a phase transition (pun very much intended) between growing *usable crystals* versus *having no crystals* (or having crystals that do not qualify as 'diffraction quality' even under the most favorable light). Points 2-9 fall into the 'I have crystals' bucket and everything else is in the 'I have no crystals' bucket.
I am being deliberately black and white of course. As to whether huge funding would help to bridge the 'phase gap' - to me this is a purely theoretical question since to the best of my knowledge there never was a 'huge funding' for this particular problem :) And if it is true that the general belief in the art is that crystallization is not worth investing into because there's no hope in it then of course it is a self-fulfilling prophesy. There is an unresolved dichotomy buried in the sentiment above: it seems that we (the community of structural biologists) more or less believe that crystallization research is not fundamentally fruitful (hence the no-funding situation). However, anyone who undertakes significant efforts to determine an actual structure using crystallography inevitably *has to* crystallize their target of interest - and therefore by definition has hope that their particular target will work out, against the overall gloomy outlook on the crystallization science as a whole. So we either are a collective of self-induced schizophrenics, or the general sentiment is wrong and systematic crystallization research is meaningful and fruitful - *just very very hard*. In ~200 BC Hannibal reportedly said "I will find a way or make one". I think that if we approach problem #1 with this attitude (and an equivalent of a very large army's worth in funding) then it can be solved. Artem - Cosmic Cats approve of this message On Sun, Jul 21, 2019 at 1:55 PM Kay Diederichs < kay.diederi...@uni-konstanz.de> wrote: > Hi Artem, > > you are certainly correct in that James' points 2-9 would be moot if his > point 1 were solved. But as long as this is not the case, we resort to work > with few and/or small and/or badly diffracting and/or non-isomorphous > crystals, which makes points 2-9 very relevant. > > Maybe the reason why crystallization research is not well funded is that > it is not expected to yield significant improvements. Personally, I think > that even huge funding would not result in methods that succeed in > crystallizing all molecules. > > best, > Kay > > On Sun, 21 Jul 2019 11:28:14 -0400, Artem Evdokimov < > artem.evdoki...@gmail.com> wrote: > > >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 > >- Cosmic Cats approve of this message > > > > > >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 > >> > >> > >> ######################################################################## > >> > >> To unsubscribe from the CCP4BB list, click the following link: > >> https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 > >> > > > >######################################################################## > > > >To unsubscribe from the CCP4BB list, click the following link: > >https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 > > > > ######################################################################## > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 > ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
