If you look at the nice figure at the top of the online article, do you believe that this (or rather, the correct) arrangement of domains/ molecules can be predicted from a couple of correlated mutations, and energy minimization? I think AI is a long way from that. Finding the correct fold of a compact domain, yes I think it's getting there.
best, Kay On Tue, 23 Jul 2019 08:28:42 +0530, Nishant Varshney <[email protected]> wrote: >What about AI doing our job in the future? > >https://www.nature.com/articles/d41586-019-01357-6?utm_source=Nature+Briefing&utm_campaign=4c1d57fdf3-briefing-dy-20190722&utm_medium=email&utm_term=0_c9dfd39373-4c1d57fdf3-44201949 > >Best Regards >Nishant > >On Mon, 22 Jul 2019 at 11:30 PM, Sarah Bowman <[email protected]> >wrote: > >> I'd like to point out that the MAchine Recognition of Crystallization >> Outcomes (MARCO) makes a start to 'deep learning applied to crystallization >> outcomes', at least in terms of being able to classify drop images >> efficiently. >> >> >> >> There is obviously more work to be done to correlate these data with >> crystallization cocktail components (which Janet and Tom point out the >> difficulties with) and positive outcomes. It seems the first step really >> needs to be consistent descriptions and vocabulary - I fully agree with >> Janet here! >> >> >> >> Reference on MARCO for those interested: Bruno AE, Charbonneau P, Newman >> J, Snell EH, So DR, Vanhoucke V, et al. (2018) Classification of >> crystallization outcomes using deep convolutional neural networks. PLoS ONE >> 13(6): e0198883. https://doi.org/10.1371/journal.pone.0198883 >> >> >> >> Cheers, >> >> Sarah >> >> >> >> *Sarah EJ Bowman, PhD* >> >> >> >> Associate Research Scientist, Hauptman-Woodward Medical Research Institute >> >> Director, High-Throughput Crystallization Screening Center >> >> Research Associate Professor, Department of Biochemistry, University at >> Buffalo >> >> >> >> Research Webpage <https://hwi.buffalo.edu/scientist-directory/sbowman/> >> >> www.getacrystal.org >> >> >> >> [email protected] >> 716-898-8623 >> >> >> >> >> >> *From: *CCP4 bulletin board <[email protected]> on behalf of Bernhard >> Rupp <[email protected]> >> *Organization: *k.k. Hofkristallamt >> *Reply-To: *"[email protected]" <[email protected]> >> *Date: *Monday, July 22, 2019 at 1:42 PM >> *To: *"[email protected]" <[email protected]> >> *Subject: *Re: challenges in structural biology >> >> >> >> What about 'deep learning' applied to crystallization outcomes? Can it >> guide individual trials better than intuition? Can it find previously >> unknown promising combinations on a larger scale? >> >> >> >> I think several people were well aware of this need for some sort of sound >> machine learning already 15 years ago but we had no cloud based AI >> >> services then....maybe it is time to pick this up - particularly if face >> recognition can classify the fine detail in faces maybe we finally could do >> this with drop images as well... >> >> >> >> A summary of the state of affairs then is here: >> >> >> http://www.ruppweb.org/cvs/br/rupp_2004_methods_predictive_models_crystallization.pdf >> >> >> >> LG BR >> >> >> >> >> >> Am 21.07.19 um 23:04 schrieb Artem Evdokimov: >> >> Dear Kay >> >> >> >> I disagree that 'magic bullet' is impossible. I think the definition is >> wrong here - magic bullet to me is a rational set of methods that (when >> executed with precision and care) enable crystallization to the maximum >> possible benefit. This includes everything - constructs, crystallization >> design, etc. Part of the magic bullet is also a precise knowledge when >> crystallization is unlikely (i.e. an actual proven predictor that >> consistently discriminates between "you're going to succeed if you work >> hard" and "it's doomed to fail, don't bother" scenarios in crystallization. >> >> The above is not sexy. It does not present itself as a lovely subject on >> which to have international cocktail parties with politicians delivering >> fancy speeches. But that is what is needed, and no one is funding that to >> the best of my knowledge. >> >> What needs to be done is a significant amount of testing, standardization, >> and methods development from the perspective of holistic outcome (i.e. >> crystals that work) - and none of the previously advertised 'magic bullets' >> work the way I just described. >> >> Having written this, I think you're right - this is a bit of a distraction >> from James' original point. However it's a valid opportunity for a lively >> discussion on its own :) >> >> Artem >> >> - Cosmic Cats approve of this message >> >> On Sun, Jul 21, 2019 at 4:52 PM Kay Diederichs < >> [email protected] <mailto:[email protected]> >> <[email protected]%3e>> wrote: >> >> Dear Artem, >> >> black or white is not my way of thinking, which is why I don't >> believe in Hannibal's approach when it comes to crystallization. >> >> None of the magic bullets that were advertised over the past decades >> have proven generally applicable. I believe more in incremental >> improvement which in this case includes a few biophysical characterization >> methods, possibly improved microfluidics or other apparatus, and expanded >> screens. And a lot of hard work, perseverance, intuition, frustration >> >> tolerance. Nothing that really needs huge funding - of course it >> does need money, but just a share of what is anyway needed for the usual >> lab work including expression, purification, functional characterization, >> binding studies and the like. >> >> One area where a huge amount of money was burnt is crystallization in >> space, on board of e.g. the spacelab and ISS. This is for me an example of >> a mis-led approach to throw money at a difficult problem, with the >> expectation of a solution. Science does not work like that, and money in >> this case seems more to be the problem than the solution. >> >> This example may illustrate a certain failure of us scientists to >> resist the temptation to promise unrealistic outcomes when confronted with >> money provided for political reasons, which ultimately undermines our >> credibility. But this takes us away from James' points. >> >> best, >> >> Kay >> >> On Sun, 21 Jul 2019 16:06:48 -0400, Artem Evdokimov < >> [email protected] <mailto:[email protected]> >> <[email protected]%3e>> wrote: >> >> >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 < >> >> >[email protected] < >> mailto:[email protected]> <[email protected]%3e>> >> 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 < >> >> >> [email protected] <mailto:[email protected]> >> <[email protected]%3e>> 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 < >> >> >> >[email protected] < >> mailto:[email protected]> >> <[email protected]%3e>> 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 >> >> > >> >> >> >> >> >> ######################################################################## >> >> >> >> 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 > ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
