Binding Terms Survey Comments
The GO consortium should remove all annotations which describe catalytic domain substrate binding, associated with catalytic activities or transport proteins, and no longer annotate these interactions.
- Terms should be annotated to binding terms only if there was an experiment that demonstrated binding. There should not be coannotation for substrate binding if an experiment demonstrates catalytic activity. Instead the catalytic annotation should be made.
- I disagree, but one should only annotate to binding if binding is directly demonstrated.
- I dissagree with the proposal. If paper has experiment for a kinase that demonstrates ATP binding, then we should annotate it. There must be an experiment since the annotation would be an IDA. What if an unknown protein is shown to bind DNA; then 5 years later, it is shown to have helicase activity. It would be counterproductive to then have to remove the first annotation.
Change the definition of 'x binding' terms to explicitly exclude catalytic domain substrate binding. Comments:
- For all the questions involving x binding redefinition, I am opposed to precomposed terms of the type "x binding"
- Do not change the definition, change annotation practice.
- When I read a paper and they show that it binds GTP, then I would like to be able to curate that fact, especially when I have no other molecular function information to give. The author is unlikely to make any unequivocal statement stating that it binds GTP but definitely doesn't hydrolyze it. And, if I have to go read other papers that do separate experiments which show that it is "NOT" hydrolyzed, can I really use the original reference as my sole source for that annotation? It seems that I have to draw an inference from multiple experiments to know that it does A (binds GTP), but definitely doesn't do B (use it as a substrate). I like to try to limit my annotations to what is directly shown by a particular experiment when possible.
- Again, binding should only be annotated if it is directly demonstrated.
- It would be an ENORMOUS amount of work to go back through annotations to decide whether the term was used 'correctly' or not
- I am not sure removing all of the "incorrect" annotations is necessary. I view it as "redundant information", which should be eliminated because it doesn't add information.
- Annotation of such binding should only be made when the experiment specifically shows such binding, when the point of the experiment is to prove such binding, not inferred by the annotator because of the presence or requirement of a cofactor or reagent in the reaction mix.
- In many older biochemistry papers, binding was used as an indicator that the protein might have catalytic activity on the binding partner. Ex: one step in the purification of a helicase might be a DNA column, but other proteins that bind to the column might not have helicase activity. It would still be useful to capture the DNA binding activity of these proteins even if they are subsequently shown to have catalytic activity on DNA. Also, it's useful to have a sense of history in GO, i.e. what was known when, so that we can see how partial information (DNA binding) might develop into a clearer picture (topoisimerase).
- I agree with all of the cons; I reject all of the pros.
- I don't see why this applies: "In future curators would not be able to annotate proteins for which the only information presented is that they bind 'x' (with no indication of the context of this binding - is it a substrate/cofactor/something else?). " If they bind 'x' then they could be annotated as such. In the future if 'x' is discovered to be a substrate, the previous annotation would have to be removed.
- I dont think it's possible to do annotation if one annotation (x binding) depends on another annotation (here, catalytic activity).
Change the definition of the' x binding' terms to explicitly exclude catalytic domain substrate binding AND make grouping terms for the activity molecular function terms to indicate the type of substrate being chemically changed (e.g. new GO term: 'catalytic activity; ATP hydrolysing')
- How is this different from ATPase activity?
- I'm sorry that I'm a bit confused by this. Is this indicating that ATP is being used to drive another reaction. Am I supposed to annotate to this term only if they prove that ATP has been hydrolyzed? If so, it seems like I still would not be able to capture a lot of "incomplete" information when this has not been tested.
- You say "in addition to the benefits associated with proposal 1..." - there were no benefits listed for proposal 1.
- I agree with the cons
- I agree with this suggestion, assuming it is possible
- I am in general in favor of trying to keep track of ATP utilizing enzymes, but am unsure of the best way to do it, nor am I sure that GO is the best place for this
Annotate to 'x binding' terms only when a gene product is found either to bind 'x' and not alter it (e.g. as a cofactor) AND when the only information available for a gene product is that they bind 'x. Comments:
- Annotate based on the experiment, not what happens to the bound substance.
- Do we have to invalidate the old curation once we do find that it hydrolyzes ATP? This was mentioned in the working group document. In a sense, if someone did a search for ATP-binding, what they would really be getting are the "ATP-binding, not further tested or curated + ATP-non-hydrolyzing" group and that doesn't seem ideal.
- Annotate to 'x binding' terms only when a gene product is found to bind 'x'. Period. Inclusion of 'either' with 'AND' in the question is confusing. I think 'OR' is intended.
- As before, annotation of such binding should only be made when the experiment specifically shows such binding, when the point of the experiment is to prove such binding, not inferred by the annotator because of the presence or requirement of a cofactor or reagent in the reaction mix.
- This makes sense: define binding as not including known catalytic activity, and define catalytic activity as including binding. To clean up the old annotations, just search for papers that annotate the same protein to both terms.
Create two 'x' binding terms: those describing substrate binding interactions and those describing cofactor binding interactions.
- I am very naive and I apologize for that. Let's say a transporter binds and hydrolyzes ATP to pump a proton. Although, technically, ATP is certainly a substrate of that transporter, is that what most users would think of as a "substrate" of a transporter? In principle, I like this distinction, but again, I worry that most authors, when showing that protein X binds Y will not tell us whether Y is acting as cofactor or a substrate. In some cases, it might be easy to infer, but, not in all cases. And how would this affect IEA annotations? Do these state whether the bound molecule acts as a cofactor or a substrate?
- I don't think this is necessary.
- Presumably there would be a parent term, e.g. ATP binding, in order for this to work. This would be my second choice if something HAS to change.
- Who needs to be told that GTPase binds GTP?
- Just annotate to what the experiment shows.
- I only agree with this solution if there is a common 'binding' parent e.g. ATP binding ---ATP binding, ATP as substrate ---ATP binding, ATP as cofactor for when you don't know what sort of binding is taking place. I don't see expansion of terms as a problem.
Create a relationship in the ontology such that if an annotation is made to a catalyst term then we also know that the gene product is annotated to a binding term for the substrates e.g. add a new relationship: 'GTP binding' involved in 'GTPase activity'.
- sorry- I'm confused.
- I prefer not to make implied annotations.
- Better to do it by definitions. See comments to #4 above.
Do nothing. Allow curators to use the existing terms that describe 'x binding' and accept that the resulting annotations will not indicate to users whether the gene product binds the molecule as a substrate or cofactor.
- Working on extended thoughts will be at http://wiki.geneontology.org/index.php/User:JimHu/Binding_terms
- Please be aware that I am answering this survey based on gut reactions with very few examples at hand and a very limited knowledge of substrate binding matters.
- It is not always straightforward to decide if the molecule is a substrate or cofactor, the author may not give all this information - we would lose a lot of information if we did not annotate these at all. Has the user community been asked about this - I can't see that they would be too perturbed to see that an ATPase had been annotated to ATP binding.
- If GTP binding is documented, it should be annotated. That might lead someone to test whether GTP is a substrate or cofactor. And anyone interested in "in vitro kinetics" or testing or assays would certainly like that information, even if it is only IEA.
- Annotators should annotate the specific data in a paper and resist the temptation to annotate binding events which are not specifically shown in the paper.
- not sure, I could be persuaded to accept this solution
- Reading through this it seems like there's a danger the solution might be worse than the problem!