Talk:Circular permutation in proteins

Preparing Extension of article
Just a quick note that Spencer Bliven and I are working on a major extension of this article, which we will try to submit to the PLoS comp biol Topics section as discussed at WP:COMPBIO and WP:MCB. --Andreas (talk) 00:25, 29 September 2011 (UTC)

The new version of the article is emerging here. We are editing outside of wikipedia, so we can license the text under a dual license (CC-by and CC-by-sa), so this is compliant both with PloS and wikipedia requirements. --Andreas (talk) 05:40, 17 November 2011 (UTC)

We're waiting on PLoS to publish the article, due to the dual license. Expect the new version to replace the one here sometime Thursday 29 March. --Quantum7 05:22, 28 March 2012 (UTC)

The article has been published now at PLoS comp biol, see also the related editorial. --Andreas (talk) 22:54, 29 March 2012 (UTC)

PLoS Comp Biol Topic Page
The existing stub was completely rewritten as part of PLoS Computational Biology's new Topic Page feature. The article was drafted on the PLoS topic page wiki, then peer reviewed and published on PLoS Comp Biol under their CC-BY-2.5 license.


 * A full version history of the rewrite can be accessed from http://topicpages.ploscompbiol.org/wiki/Circular_permutation_in_proteins.


 * Comments from the open peer-review can be viewed at http://topicpages.ploscompbiol.org/wiki/Talk:Circular_permutation_in_proteins.


 * The published article by Spencer Bliven and Andreas Prlić is available for free from http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002445.

Finally, a note on licensing. Andreas Prlić was the major author of the preexisting stub article. However, to avoid any conflict between wikipedia's CC-BY-SA-3.0 license and the PLoS CC-BY-2.5 license, the article was completely rewritten.

We enjoyed working with PLoS on improving this article, and hope that the Topic Page track will lead to many more improvements to wikipedia's coverage of computational biology.

--Spencer Bliven Quantum7 22:59, 29 March 2012 (UTC)

Open Peer Review
The version of this article that was published at PLoS comp biol underwent an open peer review process. Here what was discussed at http://topicpages.ploscompbiol.org/wiki/Talk:Circular_permutation_in_proteins. --Andreas (talk) 23:15, 29 March 2012 (UTC)

Reviews
Spencer, below you'll find Rob Russell's review. I am awaiting to hear from one other reviewer, shortly. Please await to hear from the other reviewer before implementing any changes to this page.

Review by Rob Russell
This page describes circularly permuted proteins and for the most part is a good starting point for this subject. However, I have several comments.

The first line reads "Circular permutation is a process during evolution  that changes..." I think strictly speaking it isn't an evolutionary process, but a description of the relationship between proteins that sometimes is a clear evolutionary process (sometimes a post-translational one, which I get-it is also evolutionary in some sense; at other times they are engineered as the author points out). The first permutation (concanavalin A) is more of a functional modification. I think a better opener would be to speak of it as a relationship between proteins. in other words, "Circular permutation in proteins describes the situation where one protein is circularly permuted relative to another related protein." (and then ellaborate on the other points)

I would perhaps mention that the post-translational modification of concanavalin A is a cleavage and an unusual protein-ligation (there are, I presume, suitable cross-references here too).

Re: the Swaposin story, Russell has two Ls, and I would avoid the non-wikipedia subjectivity statements like "lighthearted" - I would just say nicknamed. These are the kinds of things that get flagged in Wikipedia - the stuff has to read like an encyclopedia and not an editorial.

Re: Programmatic detection. I think this English is a bit dubious and perhaps the section would be more appropriately headed "Detection of Circular Permuations" (or similar). This section could also do with some slightly longer introduction about why it is problematic to detect these using standard techniques like dynamic programming, etc. And one reference in this list is missing which I believe to be the first method to detect permutations: Michael Zuker, JMB 221:403-420, 1991 Suboptimal sequence alignment in molecular biology: Alignment with error analysis.

The figure showing Concanavalin A and Lectin is a little hard to understand - it might be easier to use a two color (N- and C- terminus) rather than a color ramp, but perhaps this won't help - worth trying perhaps.

Review by BK Lee
Circular permutation is a process during evolution ... Concur with Robb Russell. Circular permutation is not just an evolutionary process, since it can be made in the laboratory by engineering, as the article shows later.

Circular permutation ... changes the order of amino acids ... A process that changes the order of the amino acid residues would be called simply as a permutation. Circular permutation is a particular kind of permutation, wherein the N- and C- termini of one protein is found joined together in another that is homologous.

Genetic mechanism of circular permutation One could add exon shuffling as another potential mechanism.

Among the motivations for engineering circular permutation One could mention not only the order in which it folds, but also its effect on folding kinetics (with reference to some of Howard K. Schachman's work).

"Programmatic" detection of circular permutation Concur with Robb Russell.

Instructions from Editor
Spencer, the review process is complete. Please modify your pages, provide me with details about the modifications that you introduced either by e-mail, or on the discussion page of the revised version (Don't know exactly who this works..), and send me the link to the revised version.

Response to reviewers
Thanks to Dr. Russell and Dr. Lee for their helpful reviews of our topic page. The manuscript has been significantly rewritten in response to their comments.

A full diff of the revisions made can be viewed at

Dr. Russell

 * 1) First line. The lead section has been reworded to make clear that circular permutation is a relationship between proteins. This was an excellent point, and we have striven to make clear what is being permuted more consistently throughout the article. The lead section was also changed to mention other processes which can lead to circularly permuted proteins.
 * 2) Concanavalin A mechanism. The auto-catalysis of Concanavalin A is mentioned in the PTM section, and the history section now also mentions it.
 * 3) Swaposin. Apologies for the typo in your name in this section. We have removed the word "lighthearted".
 * 4) Programmatic Detection of Circular Permutations. The section name has been expanded, and the text rewritten and expanded. Thank you for the reference to FBPLOT, which we were previously unaware of.
 * 5) Conanavalin A figure. We have rerendered this figure using a more gradual color gradient and with spheres marking the termini. This seems a little clearer to us.

Dr. Lee

 * 1) Lead section problems. The lead has been rewritten to better define circular permutation as a relationship between proteins.
 * 2) Exon shuffling. Exon shuffling is now mentioned in the evolution section as a proposed mechanism. Shuffling does seem a plausible explanation for the evolution of circular permuted proteins (although the distinction between the permutation by duplication and exon shuffling seems fuzzy at best), however we were unable to find any experimentally validated examples of exon shuffling leading to a circularly permuted protein.
 * 3) Effect on folding kinetics. References to Schachman's work have been included in the artificial CPs section

Other modifications
In addition to addressing the comments from the reviewers, the following sections were added or heavily modified. We would welcome any additional comments on these sections.


 * 1) Examples for both evolutionary mechanisms are described in detail: Saposin and Swaposin for Permutation by Duplication, and Transhydrogenases for Fission and Fusion
 * 2) Bullet points in the protein engineering section were explained in more detail, in an attempt to reduce the use of jargon.

Spencer Bliven 18:29, 14 December 2011 (PST)

Andreas Prlić 18:38, 14 December 2011 (PST)

Well done
Excellent, very well-written article, imo. It could be rewritten at a more general level in a few areas. I have not read it fully to understand the primary research issue, but this should be carefully reported, if at all, to fully comply with Wikipedia's stated standards.

A great addition to Wikipedia. Thanks for everyone who wrote or reviewed. 68.107.141.42 (talk) 15:57, 17 April 2012 (UTC)

TOPOFIT method & Self promotion
An older revision by User:Abyzov added the TOPOFIT algorithm to the algorithm list. User:U+003F promptly reverted the edit as self promotion. I think that in general, we should be forgiving of self promotion in expanding the algorithms list. For instance, the Structural alignment software contains many contributions by algorithm authors.

That said, I do not think TOPOFIT should be included in the list. The server fails to find even trivial circular permutations, such as 3P28.A vs 3AI5.A, which are 100% sequence identical and have nearly identical structures. While the paper does claim to be topologically independent, it doesn't seem to work for me for circular permutations.

--Quantum7 23:37, 11 May 2012 (UTC)