# Talk:Circular permutation in proteins

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)

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)

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 <http://en.wikipedia.org/w/index.php?title=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 [1]


#### Dr. Russell
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.
Concanavalin A mechanism. The auto-catalysis of Concanavalin A is mentioned in the PTM section, and the history section now also mentions it.
Swaposin. Apologies for the typo in your name in this section. We have removed the word "lighthearted".
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.
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
Lead section problems. The lead has been rewritten to better define circular permutation as a relationship between proteins.
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.
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.

Examples for both evolutionary mechanisms are described in detail: Saposin and Swaposin for Permutation by Duplication, and Transhydrogenases for Fission and Fusion
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)

I hope this won't discourage what you are attempting to do here, I think you're onto a useful project:

As distinct from the norms in journals, Wikipedia discourages the use of primary sources, as their selection and interpretation is itself considered a form of original research, something which we avoid as a matter of policy. This article makes extensive use of such sources. There are possible ways to remedy this. For the references which were published long ago, there are frequently other published sources that review or at least cite them, discussing the same ideas. Alternatively, primary sources may be used, with caution, being careful not to put their ideas in "the voice of the encyclopedia". Instead, they are reported as inline-attributed statements, such as Huang et al. reported on a dozen different green fluorescent proteins made by leaving out each of twelve secondary structure elements. 
Still, such statements should be used with restraint, particularly if the editors of the Wikipedia article have any connection which might impute their independence from the original work. 
Pubmed's filtering capability is a useful tool in selecting secondary sources. After querying on your subject terms, simply click on "See reviews" to show only secondary sources. This is not fail-proof, but it is helpful. LeadSongDog come howl! 21:44, 31 March 2012 (UTC)

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)

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)

This review is transcluded from Talk:Circular permutation in proteins/GA1. The edit link for this section can be used to add comments to the review.
Note to reviewers: This article was written 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. Whilst I've nominated this article in its own right, I'd also appreciate any feedback as to how these Topic Pages can be closer aligned with WP guidelines.
Reviewer: Sasata (talk · contribs) 05:49, 20 September 2012 (UTC)
I'll review this. Will need a few days to read carefully (and juggle other things). Sasata (talk) 05:49, 20 September 2012 (UTC)
Comments. Here's are some comments from a quick readthrough. I'll do a literature check and check compliance with criteria 2 and 3 soon. Sasata (talk) 17:23, 27 September 2012 (UTC)

Thanks very much. I'll get to work on your suggestions. U+003F? 08:12, 28 September 2012 (UTC)
link protein (lead sentence); antigen presentation
 Done U+003F? 08:29, 28 September 2012 (UTC)
protein homology is a more specific link than homology (biology), although the article is less developed ... your call
 Done I went with the specific, undeveloped link U+003F? 09:27, 29 September 2012 (UTC)
the lead currently doesn't function as a good summary of the article contents. See WP:Lead.
 Done I think this is a little better. U+003F? 17:56, 3 October 2012 (UTC)
It's a little short. How about adding the following to achieve a more complete summary:
the first circularly permuted protein was concanavalin A
the two main models proposed to explain the origin of these proteins
a sentence or two summary of the uses of circ perm in protein engineering
a sentence or two summary about the types of algorithms used for  detection. Sasata (talk) 07:26, 5 October 2012 (UTC)
 Done Excellent suggestions. Any better? U+003F? 15:14, 5 October 2012 (UTC)
"This method allowed for permutations to be introduced at arbitrary sites, and is still used today to design circularly permuted proteins in the lab." source?
 Done Couldn't find a ref for the second half of this statement – removed. U+003F? 14:37, 3 October 2012 (UTC)
"Saposin and swaposin were the first known case of two natural genes related by a circular permutation." source?
 Done U+003F? 10:03, 30 September 2012 (UTC)
"The Circular Permutation Database[8] contains 2,238 circularly permuted protein pairs with known structures, and many more are known without structures." I imagine this number will change, so perhaps "As of" would be useful here. Also, there shouldn't be an outgoing link in the article text.
 Done U+003F? 09:27, 29 September 2012 (UTC)
Citation for the "exon shuffling" mechanism?
 Done U+003F? 10:22, 30 September 2012 (UTC)
In the "permutation by duplication mechanism" image (and accompanying text), it's not clear to me how the insertion of start/stop codons would cause the order of the genes to be swapped. Also, what does the "in place" part of "First, a gene is duplicated in place." mean?
 Done Make more sense? U+003F? 14:37, 3 October 2012 (UTC)
Much better! I added an additional clarification. Sasata (talk) 07:26, 5 October 2012 (UTC)
"For a review on functional and structural features of saposin-like proteins, see Bruhn (2005).[17]" This type of reference isn't usual for a Wikipedia article. More common would be to put this in this "Further reading" section, or even better, to use the article as a source and cite it directly.
 Done I pulled this sentence (but kept the reference). U+003F? 14:37, 3 October 2012 (UTC)
"Both consist of 4 alpha helices ..." spell out numbers less than 10, per WP:MoS
 Done U+003F? 08:29, 28 September 2012 (UTC)
possibly useful links: ortholog; phylogenetic analysis; restriction enzyme; ligase; substrate specificity; protein folding; calmodulin; florescence; protein topology
 Done U+003F? 09:27, 29 September 2012 (UTC)
not sure if the wiktionary link to "fission" is that useful
 Done U+003F? 08:29, 28 September 2012 (UTC)
"less accessible termini" -> "less-accessible termini"
 Done U+003F? 08:29, 28 September 2012 (UTC)
would like to see citations for the first paragraphs of "Algorithmic detection of circular permutations
 Done U+003F? 14:37, 3 October 2012 (UTC)
suggested wikilinks in the table: dot plot; geometric hashing; Ramachandran sequential transformation (is Ramachandran plot relevant?)
 Done U+003F? 12:22, 29 September 2012 (UTC)
the "See also" link to cyclic permutation is redundant, as it is already linked in the lead
 Done U+003F? 08:29, 28 September 2012 (UTC)
the references could use a bit of tidying; this is beyond GA-level requirements, so feel free to ignore (although I may clean them up myself in that case!)
journal titles should be in title case consistently (and please fix the ALL CAPS in Cheltsov 2001)
 Done U+003F? 10:01, 29 September 2012 (UTC)
similarly, journal article titles should be consistently in either title or sentence case (the latter is more usual)
 Done U+003F? 10:01, 29 September 2012 (UTC)
3.0-A -> 3.0-Å
 Done U+003F? 08:29, 28 September 2012 (UTC)
"Correct folding of circularly permuted variants of a beta alpha barrel enzyme in vivo" -> "... of a βα barrel ..."
 Done U+003F? 08:29, 28 September 2012 (UTC)
Qian 2005 needs the species name italicized
 Done U+003F? 08:29, 28 September 2012 (UTC)
Beernink et al. 2001, change alpha to α
 Done U+003F?
Thanks again. I've had a first pass at dealing with your comments and suggestions. Let me know what you think. U+003F? 17:56, 3 October 2012 (UTC)

I've had a look at the recent literature in this topic and am confident that the article meets the criteria 3a ("addresses the main aspects of the topic") and 3b ("stays focused on the topic without going into unnecessary detail"). I've also verified several of the statements in the article and think the article complies with criteria 2a, b, and c. The images all have Wikipedia-compatible licenses. I'll be happy to promote to GA once the last issue with the lead is addressed. Sasata (talk) 07:26, 5 October 2012 (UTC)
Ok, all of my concerns have been resolved satisfactorily, and I am confident that the article meets the GA criteria. Good working with you, and I hope to see more of these computational biology topic pages here at GAN! Sasata (talk) 03:09, 6 October 2012 (UTC)