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
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" <CCP4BB@JISCMAIL.AC.UK im Auftrag von
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 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
<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 GrÃπne <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
>>>>>>>>
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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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>>>>>>
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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
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>>>>>
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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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