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, [email protected] 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, [email protected] <[email protected]>
>>>> 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 <[email protected]> On Behalf Of Nukri
>>>>> Sanishvili
>>>>> Sent: 15 July 2019 23:09
>>>>> To: [email protected]
>>>>> 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 <[email protected]
>>>>> <mailto:[email protected]> > 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 <[email protected]
>>>>>>> <mailto:[email protected]> > 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
>>>>>>>> ########################################################################
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>>>>>>>
>>>>>>> --
>>>>>>> --
>>>>>>> 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
>>>>>>>
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>>>>>> To unsubscribe from the CCP4BB list, click the following link:
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>>>>>>
>>>>>
>>>>>
>>>>> --
>>>>> 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
>>>>>
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>>>>>
>>>>>
>>>>>
>>>>> _____
>>>>>
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>>>>
>>>>
>>>> --
>>>> 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
>>>>
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>>>
>>
>>
>> --
>> 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
>>
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>
>


-- 
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

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