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Reviewer 1: Dr. R. Russell

Posted by PLOS_CompBiol on 30 Mar 2012 at 09:24 GMT

[This is a review of the original version - see Text S1 for the version history]

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.

No competing interests declared.

RE: Reviewer 1: Dr. R. Russell [Author Response]

PLOS_CompBiol replied to PLOS_CompBiol on 30 Mar 2012 at 09:30 GMT

[These are the author responses, which are reflected in the published version]

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.

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.

No competing interests declared.