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 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 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 <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> On Behalf Of Nukri >>>> Sanishvili >>>> Sent: 15 July 2019 23:09 >>>> To: 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> > 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> > 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
