Hi James, Related to Joel's post, how does on interpret the wealth of structural data we already have comprehensively. If you have 30 structures of the same protein in slightly different states, how do you inspect the differences?
Cheers, Roobie On 17 Jul 2019 13:44, Joel Sussman <joel.suss...@weizmann.ac.il> wrote: Dear James Another key point, which is directly related to the discussion of 'why' one does a particular structural study, is: how one explains the results to others, including even to 'non structural biologists’. This is important and INDEPENDENT of the particular experimental procedure. Some examples of possible ways to this can be seen in Proteopedia, e.g. * Insulin - http://proteopedia.org/w/Insulin * Tutorial:How do we get the oxygen we breathe - http://proteopedia.org/w/Tutorial:How_do_we_get_the_oxygen_we_breathe * Immunodeficiency virus protease - http://proteopedia.org/w/Immunodeficiency_virus_protease * An Interactive 3D Complement to a 'Molecular Cell' paper - http://proteopedia.org/w/Journal:Molecular_Cell:1 Joel -------------------------------------------------------------------------------- Prof. Joel L. Sussman joel.suss...@weizmann.ac.il<mailto:joel.suss...@weizmann.ac.il> www.weizmann.ac.il/~joel<http://www.weizmann.ac.il/~joel> Dept. of Structural Biology tel: +972 (8) 934 6309 proteopedia.org<http://www.weizmann.ac.il/~joel> Weizmann Institute of Science fax: +972 (8) 934 6312 Rehovot 76100 ISRAEL mob: +972 (50) 510 9600 --------------------------------------------------------------------------------- On 17Jul, 2019, at 13:00, Susan Lea <susan....@path.ox.ac.uk<mailto:susan....@path.ox.ac.uk>> wrote: I'll shut up soon Other than when asked to review, I consider it best to concern myself most with how I use the share of the limited resources I have access to and refrain from commenting on work by others in fields I have sufficiently little knowledge of that my estimate of worth is likely to be flawed. I certainly do not agree that a structure determined by EM is a priori more biologically true than one determined by crystallography - as always the only question is exactly what is the structure of, and how has the sample had to be compromised to determine it. If you feel you can prove that this is a flawed statement across the whole of biology - publish an article and we can shut the synchrotrons. Yours - from a mixed-method structural biologist ;-) Susan Prof. Susan M. Lea, FMedSci tel: +44 1865 275181 ------------------------------------------------------------------------------------------ Director of the Central Oxford Structural Microscopy and Imaging Centre & Professor of Microbiology Sir William Dunn School of Pathology, Oxford OX1 3RE Professorial Fellow @ WadhamCollege ________________________________________ From: 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>> Sent: 17 July 2019 10:21:42 To: Susan Lea Cc: ccp4bb@jiscmail.ac.uk<mailto:ccp4bb@jiscmail.ac.uk> Subject: Re: [ccp4bb] challenges in structural biology 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 don’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. Let’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 Grüne <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 ________________________________ 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
