[Go] 'binding issues' item listed on the GO Consortium meeting agenda
Jim Hu
jimhu at tamu.edu
Mon Mar 23 15:55:59 PDT 2009
Hi all,
I think this particular case should be ok as long as we have some way
of handling the is_conjugate_acid and is_conjugate_base
relationships. "phosphoenolpyruvic acid" and "phosphoenolpyruvate"
interconvert in water, and very few papers will be able to distinguish
which form is the actual ligand. I think that this means that
curators would correct to annotate to either, and reasoners will have
to know that annotations to one are equivalent to annotations to the
other. Note that the conjugate acid/base business here actually
understates the chemical heterogeneity, as the phosphate group in PEP
is treated in ChEBI as if it doesn't titrate. My colleagues point out
that this doesn't even touch on things like Mg-ATP vs ATP; adenylate
kinase uses one of each!
For most annotation, we don't care which form is used, as long as they
meet some criterion for being chemically "the same". For me, that
would be having the same covalent structure and considering titratable
groups that dissociate easily in water as noncovalently bound. So,
for annotation, I suppose I'd prefer a single term that merged
"phosphoenolpyruvic acid" and "phosphoenolpyruvate"
But ChEBI isn't set up that way. In principle, I suppose we could
make a ChEBI slim for GO that only has the dominant form at
physiological pH? Or we could ask the ChEBI people to change?
Did that make sense?
The functional parentage relationship is fundamentally very different,
and true path does emphatically not apply. The functional parent of
PEP (both forms) is acrylate/acrylic acid, which lacks the phosphate.
The covalent structure is different. Some examples that might fall
under what Harold is thinking about might be: dUTP vs dTTP for DNA
polymerase, or Isoleucine vs Valine for aminoacyl-tRNA synthetases.
In both cases, the single methyl group can only provide a small amount
of difference in binding energy - which still gives a difference in
affinity on the order of 100-fold. Misincorporation in the absence of
proofreading is evidence that these alternate substrates can bind, but
I don't think I would annotate valine binding to Ile-aaRS or dUTP
binding to DNA polymerase.
Would people annotate azaC binding to reverse transcriptase? I
wouldn't, but perhaps some would?
Jim
On Mar 23, 2009, at 4:25 PM, Harold Drabkin wrote:
> From one of Jim's earlier comments, I think a big problem is
> parentage: if Chebi has a relationship between, say glucose-6
> phosphate and glucose (child parent or something) , and we have a
> protein that binds glucose-6-phosphate, we don't want to imply any
> binding to glucose ( it might, but it might not). Chebi may have
> relationships between, for example, for ATP, ADP, and AMP, but a
> protein may bind very specifically to one of them. And I suppose
> there are many cases where a protein can bind related chemicals with
> different non-zero affinities, so that if one annotated binding to
> one there may be a good chance it would bind another. Should there
> be a rule in how one interprets the annotation line so as to not
> read any relationships among things in the target ontology to the
> actual single term designated as the target for the GO annotation?
> (hope this is clear).fcc
>
> Harold
>
>
>
> Chris Mungall wrote:
>> I have added this example to the col16 page:
>> http://wiki.geneontology.org/index.php/Annotation_Cross_Products#Binding
>>
>> I think the use of CHEBI in annotation-time cross-products poses
>> specific problems
>>
>> * It's often not clear (to me anyway) which CHEBI term to use.
>> Jim's example (linked to in the above page) has "PEP binding".
>> CHEBI has two terms in which PEP is a RELATED synonym:
>> "phosphoenolpyruvic acid" and "phosphoenolpyruvate". neither of
>> these are defined in the traditional OBO sense. It's not clear if
>> the InChi strings count as they are under RELATED synonym too.
>>
>> (Jim/Debbie - since you provided this example can you comment on
>> this, I'm too lazy to read the PMID, thanks!)
>>
>> * Many CHEBI terms do not have is_a parents. It's extremely
>> important for there to be correct is_a parentage. For example, if
>> the post-composed term is "phosphoenolpyruvic acid binding" then
>> this can be inferred to be a subtype of GO:0042301 ! phosphate
>> binding, based on is_a parentage in CHEBI.
>>
>> * CHEBI has other relations, but their semantics are unclear
>>
>> This gives me reason for caution. However, I am optimistic - CHEBI
>> are willing to fix these things in their ontology.
>>
>> In particular I would propose the following guidelines for use of
>> CHEBI in annotation time cross-products
>>
>> * The CHEBI term *should* preferably have a definition. The GO
>> annotator who uses a CHEBI ID in col 16 should propose a definition
>> on the CHEBI tracker
>> * The CHEBI term *must* have is_a ancestry to CHEBI:24431 !
>> molecular structure. If a GO annotator wishes to use a CHEBI ID in
>> col 16, and there is no such ancestry, the annotator should send a
>> request on the CHEBI tracker
>> * The CHEBI term *should* have the correct synonym assignment. For
>> example, if the GO curator thinks the correct post-composed term is
>> "PEP binding" then PEP *must* be either an EXACT synonym or a
>> primary term name.
>>
>> On Mar 18, 2009, at 7:53 AM, Jim Hu wrote:
>>
>>> Hi Pascale,
>>>
>>> I think this is also potentially related to the discussion of
>>> whether/how the cross-product system can/should be used for post-
>>> composition of binding annotations.
>>>
>>> Jim
>>>
>>> On Mar 18, 2009, at 8:46 AM, Pascale Gaudet wrote:
>>>
>>>> Hi Emily,
>>>>
>>>> I am attaching the summary Debby Siegele put together about some
>>>> of the issues we've been having with substrate binding. (This was
>>>> sent to the ref genome list).
>>>>
>>>> Pascale
>>>>
>>>> Emily Dimmer wrote:
>>>>>
>>>>> Hi,
>>>>>
>>>>> I noticed that the GO Consortium meeting agenda for Monday 30th
>>>>> March has a item entitled 'binding issues'. However there is no
>>>>> indication of who added this topic.Could someone please give a
>>>>> bit more detail about why this item has been added?
>>>>>
>>>>> I do agree that it is an area that is probably worth discussing
>>>>> (particularly with regards ISSing 'protein binding'
>>>>> annotations). Its just that I feel that agenda items which deal
>>>>> with annotation issues are more easily resolved when the meeting
>>>>> participants have had advanced notice as to the background of
>>>>> the discussion topic, so to be able to review their database's
>>>>> annotation sets/collect their thoughts!
>>>>>
>>>>> Thanks,
>>>>> Emily
>>>>>
>>>>>
>>>>>
>>>>> ------------------------------------------------------------------
>>>>> Emily Dimmer Ph.D.
>>>>> GOA Coordinator
>>>>> EMBL-EBI
>>>>> Wellcome Trust Genome Campus
>>>>> Hinxton
>>>>> Cambridge CB10 1SD, U.K.
>>>>> Tel: +44 1223 494654
>>>>> Fax: +44 1223 494468
>>>>> email: edimmer at ebi.ac.uk
>>>>> URL: http://www.ebi.ac.uk/goa
>>>>>
>>>>> _______________________________________________
>>>>> Go mailing list
>>>>> Go at geneontology.org
>>>>> http://fafner.stanford.edu/mailman/listinfo/go
>>>>>
>>>>>
>>>> <
>>>> BindingTermDocumentation
>>>> .doc>_______________________________________________
>>>> Go mailing list
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>>>
>>> =====================================
>>> Jim Hu
>>> Associate Professor
>>> Dept. of Biochemistry and Biophysics
>>> 2128 TAMU
>>> Texas A&M Univ.
>>> College Station, TX 77843-2128
>>> 979-862-4054
>>>
>>>
>>> _______________________________________________
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>>
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>
=====================================
Jim Hu
Associate Professor
Dept. of Biochemistry and Biophysics
2128 TAMU
Texas A&M Univ.
College Station, TX 77843-2128
979-862-4054
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