Re: [ccp4bb] The importance of USING our validation tools

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CCP4bb <-- 1999 <-- November 1999 <-- 30 November 1999

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Subject: NSCM keyword in MolRep
From: Cynthia Czyrphony cynthia {- dot -} czyrphony {- at -} GMAIL {- dot -} COM
Date: 2007-08-16

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Subject: Re: The importance of USING our validation tools
From: Phil Evans pre {- at -} MRC-LMB {- dot -} CAM {- dot -} AC {- dot -} UK
Date: 2007-08-16

Subject: Re: The importance of USING our validation tools
From: Ashley Buckle ashley {- dot -} buckle {- at -} MED {- dot -} MONASH {- dot -} EDU {- dot -} AU
Date: 2007-08-16

Dear Randy

These are very valid points, and I'm so glad you've taken the
important step of initiating this. For now I'd like to respond to one
of them, as it concerns something I and colleagues in Australia are
doing:
>
> The more information that is available, the easier it will be to
> detect fabrication (because it is harder to make up more
> information convincingly). For instance, if the diffraction data
> are deposited, we can check for consistency with the known
> properties of real macromolecular crystals, e.g. that they contain
> disordered solvent and not vacuum. As Tassos Perrakis has
> discovered, there are characteristic ways in which the standard
> deviations depend on the intensities and the resolution. If
> unmerged data are deposited, there will probably be evidence of
> radiation damage, weak effects from intrinsic anomalous scatterers,
> etc. Raw images are probably even harder to simulate convincingly.

After the recent Science retractions we realised that its about time
raw data was made available. So, we have set about creating the
necessary IT and software to do this for our diffraction data, and
are encouraging Australian colleagues to do the same. We are about a
week away from launching a web-accessible repository for our recently
published (eg deposited in PDB) data, and this should coincide with
an upcoming publication describing a new structure from our labs. The
aim is that publication occurs simultaneously with release in PDB as
well as raw diffraction data on our website. We hope to house as much
of our data as possible, as well as data from other Australian labs,
but obviously the potential dataset will be huge, so we are trying to
develop, and make available freely to the community, software tools
that allow others to easily setup their own repositories. After
brief discussion with PDB the plan is that PDB include links from
coordinates/SF's to the raw data using a simple handle that can be
incorporated into a URL. We would hope that we can convince the
journals that raw data must be made available at the time of
publication, in the same way as coordinates and structure factors.
Of course, we realise that there will be many hurdles along the way
but we are convinced that simply making the raw data available ASAP
is a 'good thing'.

We are happy to share more details of our IT plans with the CCP4BB,
such that they can be improved, and look forward to hearing feedback

cheers
Ashley Buckle and James Whisstock

>
> If a structure is fabricated by making up a new crystal form,
> perhaps a complex of previously-known components, then the crystal
> packing interactions should look like the interactions seen in real
> crystals. If it's fabricated by homology modelling, then the
> internal packing is likely to be suboptimal. I'm told by David
> Baker (who knows a thing or two about this) that it is extremely
> difficult to make a homology model that both obeys what we know
> about torsion angle preferences and is packed as well as a real
> protein structure.
>
> I'm very interested in hearing about new ideas along these lines.
> The wwPDB has agreed to sponsor a workshop next year where we will
> propose and test new validation criteria.
>
> 4. If new validation criteria are applied at the PDB, won't someone
> who wants to fabricate a structure just keep improving their
> fabricated model until it passes all the tests?
>
> That's a possibility, but I think the deterrence effect of knowing
> that there are measures to detect fabrication will outweigh this.
> And it isn't enough for a fabricated structure to pass today's
> tests; it has to pass all the new tests devised for the rest of the
> person's life, or at least their career.
>
> 5. What should we do if tests suggest that a structure may be
> fabricated?
>
> I think we need to be extremely careful. Conclusions should not be
> drawn on the basis of a few numbers. The tests can just point up
> which structures should be examined closely. Close examination
> would then involve less automated criteria, such as whether the
> structure agrees with all the biochemical data about the system. As
> in the process followed by Nature, you also have to start by giving
> the people who deposited the structure an opportunity to explain
> the anomalies.
>
> Randy Read

*NOTE* My new tel. no: (03) 9902 0269

Ashley Buckle Ph.D
NHMRC Senior Research Fellow
The Department of Biochemistry and Molecular Biology
School of Biomedical Sciences, Faculty of Medicine &
Victorian Bioinformatics Consortium (VBC)
Monash University, Clayton, Vic 3800
Australia

http://www.med.monash.edu.au/biochem/staff/abuckle.html
iChat/AIM: blindcaptaincat
skype: ashley.buckle
Tel: (613) 9902 0269 (office)
Tel: (613) 9905 1653 (lab)

Fax : (613) 9905 4699

CCP4bb navigation

CCP4bb <-- 1999 <-- November 1999 <-- 30 November 1999

Previous message:
Subject: NSCM keyword in MolRep
From: Cynthia Czyrphony cynthia {- dot -} czyrphony {- at -} GMAIL {- dot -} COM
Date: 2007-08-16

Next message:
Subject: Re: The importance of USING our validation tools
From: Phil Evans pre {- at -} MRC-LMB {- dot -} CAM {- dot -} AC {- dot -} UK
Date: 2007-08-16