Dear all While I am well aware as are many that complimentary methods offer a great deal these days, I think X ray diffraction is not a solved problem for the reasons originally enumerated by James amongst others
I would also remind that the conference is Diffraction Methods in Structural Biology And is unique in being a conference where us methods types can get together and exchange ideas. I for one would be disappointed if it became a biology results only conference focussed on non diffraction methods. While I recognise the value that these methods bring, no one technique rules them all, which applies to X ray diffraction as much as any other There are dedicated GRCs for EM etc. Best wishes Graeme On 17 Jul 2019, at 12:36, Bärbel Blaum <baerbel.bl...@intherabio.com<mailto:baerbel.bl...@intherabio.com>> wrote: Dear all, I totally agree with Radu. James was not entirely clear if he wanted to exclusively cover challenges "faced during structure determination" or, maybe more generally, "challenges faced by structural-biologists", which makes a big difference in the eyes of some of us. Now for the actual scientific part of the meeting it might be best to concentrate on the first type of challenges, since there are plenty. However, since Gordon conferences attract a number of young participants who have not yet decided where to go I would think it is an excellent place to openly discuss those broader-perspective type of questions as well. Non-structural biology techniques that are closer to the real thing (like microscopy) have gained a lot of ground as well, and while it might be incomprehensive for some of us why anyone would choose any biological discipline other than structural biology I am under the stark impression that some students have indeed already started to regard crystallography as a dinosaur technique, and not just because cryoEM improved - that is a challenge to structural biology, too. Kind regards, Bärbel -- Bärbel Blaum, PhD Inthera Bioscience AG Einsiedlerstrasse 34 CH-8820 Waedenswil Switzerland E-Mail: baerbel.bl...@intherabio.com<mailto:baerbel.bl...@intherabio.com> Phone: +41 43 477 94 72-- Am 17.07.19, 11:53 schrieb "CCP4 bulletin board im Auftrag von r...@mrc-lmb.cam.ac.uk<mailto:r...@mrc-lmb.cam.ac.uk>" <CCP4BB@JISCMAIL.AC.UK<mailto:CCP4BB@JISCMAIL.AC.UK> im Auftrag von r...@mrc-lmb.cam.ac.uk<mailto:r...@mrc-lmb.cam.ac.uk>>: Hi Paul, Fair point, apologies if anyone was offended by my comments! I simply thought that such matters are meaningful for this forum. I am just as guilty as everyone, and it is important to put our work into the broader perspective from time to time. Best wishes, Radu Hi Radu and all Could i humbly suggest some careful reflection before this ends up polarising the amazing structural biology community. Since the year dot everyone has been contributing to integrated approaches and I fear that the tone of this debate will create much negativity around the community which seems pointless at least to me.. Maybe a commentary published somewhere would be a better way to debate what are important issues and not through the CCP4 forum? best wishes Paul On 17 Jul 2019, at 10:21, r...@mrc-lmb.cam.ac.uk<mailto:r...@mrc-lmb.cam.ac.uk> wrote: Hi Susan, We are not naive if we care about using the limited resources of this planet responsibly. This has nothing to do with whoever's favourite method. I have nothing against crystallography, it is a beautiful art and has been a success historically. I have solved plenty of crystal structures myself and will probably have to keep doing it for a little while. But it is naive to ignore that the time to move on has arrived, and that we have to use resources to develop better technologies which address the real biological questions instead of keeping dinosaurs on life support. How many of the structures solved on synchrotrons worldwide and of the zillions in the PDB are of any use or biological relevance (original question)? There is an enormous amount of waste, including the nasty chemicals use to grow crystals and to phase pointless structures, let's be honest. Best wishes, Radu I think we are naive if we care about the method used to obtain the structure - what matters is getting at the structure. What is great is that the variety of ways we can do this has increased meaning more samples become tractable for high resolution structure determination. I donâ•˙t see the point of ridiculous my method is better than your method arguments - for some samples all methods are equivalent, for some there is only one method that will yield answers - we just need to train students and develop methods that allow the broadest access. Everything else is bias-driven posturing. Letâ•˙s just solve some structures and learn something about biology. Susan Sent from my iPhone On 17 Jul 2019, at 08:43, r...@mrc-lmb.cam.ac.uk<mailto:r...@mrc-lmb.cam.ac.uk> <r...@mrc-lmb.cam.ac.uk<mailto:r...@mrc-lmb.cam.ac.uk>> wrote: Hi Both, I am not questioning the PDB stats, the issue was whether (crystal) structures are sufficiently relevant to address biological questions and justify the resources. Fragment screening is one example where investment in protein crystallography can still be justified (for now). But it doesn't really ask or answer biological questions... for these, whether we like it or not, macromolecular crystallography (or NMR, even in cell) cannot be the future. In my opinion :-) Best wishes, Radu Stating the crystallography is dead might be a bit premature, it is still king for depositions. In 2017 we had a large number of fragment screening experiments deposited. From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK<mailto:CCP4BB@JISCMAIL.AC.UK>> On Behalf Of Nukri Sanishvili Sent: 15 July 2019 23:09 To: CCP4BB@JISCMAIL.AC.UK<mailto:CCP4BB@JISCMAIL.AC.UK> Subject: Re: [ccp4bb] challenges in structural biology I know it is going to hijack the original topic but I could not help... ╲The reports of death of (macromolecular) crystallography are greatly exaggerated. If we believed the prognosticators, it has been dead since the 80s when some folks made the claim that the only relevant structures were those solved by NMR. I think we've done quite well since then... Best, Nukri On Mon, Jul 15, 2019 at 3:45 PM <r...@mrc-lmb.cam.ac.uk<mailto:r...@mrc-lmb.cam.ac.uk> <mailto:r...@mrc-lmb.cam.ac.uk> > wrote: Hi Tassos, Tim, I wonder why would you or anyone on this list worry whether biological questions that can be asked and answered with structures are relevant to justify the resources? I think there is abundant evidence that this is the case. Unless your point is that crystallography is now dead for all practical purposes... then yes, I fully agree :-) It would however be wrong to erase its historical contribution to understanding biology. Best wishes, Radu I would wonder more if the biological questions you can *ask* with a (crystal) structure are sufficiently relevant to justify the resources. Sent from my iPhone On 15 Jul 2019, at 22:08, Tim GrÃπne <tim.gru...@univie.ac.at<mailto:tim.gru...@univie.ac.at> <mailto:tim.gru...@univie.ac.at> > wrote: 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 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB <https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1> &A=1 -- -- 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 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB <https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1> &A=1 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB <https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1> &A=1 -- Radu Aricescu MRC Laboratory of Molecular Biology Francis Crick Avenue Cambridge Biomedical Campus Cambridge CB2 0QH, U.K. tel: +44-(0)1223-267049 fax: +44-(0)1223-268305 www: http://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/radu-aricescu ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB <https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1> &A=1 _____ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB <https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1> &A=1 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 -- Radu Aricescu MRC Laboratory of Molecular Biology Francis Crick Avenue Cambridge Biomedical Campus Cambridge CB2 0QH, U.K. tel: +44-(0)1223-267049 fax: +44-(0)1223-268305 www: http://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/radu-aricescu ######################################################################## 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 -- Radu Aricescu MRC Laboratory of Molecular Biology Francis Crick Avenue Cambridge Biomedical Campus Cambridge CB2 0QH, U.K. tel: +44-(0)1223-267049 fax: +44-(0)1223-268305 www: http://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/radu-aricescu ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 -- Radu Aricescu MRC Laboratory of Molecular Biology Francis Crick Avenue Cambridge Biomedical Campus Cambridge CB2 0QH, U.K. tel: +44-(0)1223-267049 fax: +44-(0)1223-268305 www: http://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/radu-aricescu ######################################################################## 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 -- This e-mail and any attachments may contain confidential, copyright and or privileged material, and are for the use of the intended addressee only. 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