Dear all,
this is by far not the general case in our hands. Depending on which
AlphaFold protocol is used, the resulting models have locally disfavourable
geometries–including clashes–, impossible chain crossovers, etc. I would
definitively recommend everybody to go through the model in detail and
perform
a final geometry minimization with Coot and/or Phenix/Refmac. And in
these cases, general geometry validation as provided by MolProbity
provides a final proof of the computational model.
Best,
Xavier
-------- Forwarded Message --------
Subject: Re: [ccp4bb] Validation of structure prediction
Date: Tue, 21 Dec 2021 09:43:37 +0000
From: Vollmar, Melanie (DLSLtd,RAL,LSCI)
<000064fe7ccc6b4d-dmarc-requ...@jiscmail.ac.uk>
Reply-To: Vollmar, Melanie (DLSLtd,RAL,LSCI)
<melanie.voll...@diamond.ac.uk>
To: CCP4BB@JISCMAIL.AC.UK
Tristan is spot on. All the predicted structures have near perfect
geometry, so commonly used validation tools like MolProbity can no
longer be applied.
What you need to consider is biological relevance of the predicted
model. Does the model correctly reflect residue arrangement in the
active site? Are domains in correct relative orientation to allow for
interactions and movements, perhaps found by some other assay? Is there
appropriate room to fit a ligand/cofactor? Are transmembrane helices, if
there are any, correctly found?
You need to map the knowledge you have of your protein to the structure
and see if the atom positions and what you know support each other.
Cheers
M
------------------------------------------------------------------------
*From:* CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of Tristan
Croll <ti...@cam.ac.uk>
*Sent:* 21 December 2021 08:28
*To:* CCP4BB@JISCMAIL.AC.UK <CCP4BB@JISCMAIL.AC.UK>
*Subject:* Re: [ccp4bb] Validation of structure prediction
I agree with Dale. Tools like MolProbity are not the right approach to
validating a structure prediction. To understand why, just consider that
all you need to do to get a perfect MolProbity score is predict every
structure as a single long alpha helix with ideal rotamers, with a kink
at each proline.
To validate a predicted structure will require a completely different
toolset - one that I’m not sure fully exists yet.
— Tristan
> On 20 Dec 2021, at 18:47, Dale Tronrud <de...@daletronrud.com> wrote:
>
> I don't see any reason to believe that software designed to
validate crystallographic or NMR models would have any utility
validating AlphaFold predicted models. Doesn't the prediction software
already ensure that all the indicators used by Molprobity are obeyed?
I'm afraid that the tools to validate any new technique must be designed
specifically for that technique. (And when they become available they
will be useless for validating crystallographic models!)
>
> Dale E. Tronrud
>
>> On 12/20/2021 10:28 AM, Nicholas Clark wrote:
>> The Molprobity server can be run online and only requires the
coordinates in PDB format: http://molprobity.biochem.duke.edu/
<http://molprobity.biochem.duke.edu/>.
>> Best,
>> Nick Clark
>> On Mon, Dec 20, 2021 at 11:10 AM Reza Khayat <rkha...@ccny.cuny.edu
<mailto:rkha...@ccny.cuny.edu <mailto:rkha...@ccny.cuny.edu>>> wrote:
>> Hi,
>> Can anyone suggest how to validate a predicted structure? Something
>> similar to wwPDB validation without the need for refinement
>> statistics. I realize this is a strange question given that the
>> geometry of the model is anticipated to be fine if the structure was
>> predicted by a server that minimizes the geometry to improve its
>> statistics. Nonetheless, the journal has asked me for such a report.
>> Thanks.
>> Best wishes,
>> Reza
>> Reza Khayat, PhD
>> Associate Professor
>> City College of New York
>> Department of Chemistry and Biochemistry
>> New York, NY 10031
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>> --
>> Nicholas D. Clark
>> PhD Candidate
>> Malkowski Lab
>> University at Buffalo
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