Talk:Cyclol

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Contents 1 General comments 2 Peer reviewer output 3 Proposal for new "scientific method section" 3.1 Comments

[edit] General comments

Willow, you've done a great job with this article. (Did we really not have an article on the subject before? Wow.) As a general thought, the headings are rather long and wordy; ie, the first one could be just "historical context" or similar. Subsections are also nice - I use very high resolution and the text still looks a bit blocky, so I imagine the text blocks look even longer and denser to most readers. Other thoughts:

• I don't have a strong opinion on the list in the lead, but I bet it'll get complaints at a FAC.
• Labeling figures as "figure 1", etc sounds sensible, but just makes it more difficult to reorganize later if you add or move an image and then have to go chasing down all the subsequent numbers. I wish we had LaTeX-style labels but I suppose those would just get borked up eventually too.
• There are multiple times when Dorothy Wrinch is referred to as "Dr. Wrinch", but everybody else just gets a last name. Any reason?
• There's a few words that stand out as 'this doesn't belong' - "Unfortunately, the Langmuir-Wrinch hypothesis...", "unscientific rejection of its elements..."
• Piles of 3 or more citations for a single statement could be condensed into one footnote with multiple papers listed.
• The end section says "The cyclol model was the first hypothesis for the structure of globular proteins" but the initial history section implies that other models for proteins were extant when the cyclol model was proposed.
• More on those naturally occurring cyclol bonds would be useful - even an image of one of these peptides with the cyclol bond highlighted.
• Did Wrinch ever retract the cyclol model or publish anything acknowledging its failure?
• I'm not sure how much the rejection of the hydrophobic folding model along with the cyclol model really means ("unscientific rejection...") - at the time it wasn't clear that the hydrophobicity idea had legs to stand on outside the cyclol model.
• In fig. 3, maybe put the hydrogens on the hydroxyls? Might be easier to look at and know they aren't peptide carbonyls. (fig4, though, is very cool-looking as it is.)
• Two-column format for the references?

Opabinia regalis 03:15, 3 November 2006 (UTC)

You're such a gem — thanks! You're totally right on every count although, for some, I'm not quite sure what to do. The easiest ones to fix are those a little embarassing to me, little outcroppings of feeling rather than cool-headed encyclopedic professionalism. The "Dr. Wrinch" penchant is, I think, me being subconsciously defensive of her, which is silly and unreasonable, given how long ago that all was. The same is true of the "unfortunately" and whatnot although, there, my loyalty is to the field of protein science. Thanks for making me aware of my POV; it's not always easy to see, although it should be easy to fix.

To my knowledge, the cyclol model was the first structural model of globular proteins, rather than a theory about its chemical composition. Astbury had some ideas about the alpha and beta structures in fibrous proteins but I don't believe that he really specified atomic positions or even that fibrous protein structures such as the alpha helix would appear in globular proteins. I guess that most protein scientists were shy of making models on so few data.

I don't think Wrinch ever retracted her theory in print; her attitude was more of "well, even if this exact model is incorrect, features of it may well be observed in globular proteins". Peptide cyclolization and the beautiful regularity/symmetry of her model seemed to exert a powerful hold on her imagination; she seemed to find it hard to believe that Nature could pack atoms tightly but irregularly, and that proteins could be so, well, sloppy and floppy. The affectionate obituary by Dorothy Crowfoot suggests that she couldn't relinquish hope for her theory altogether.

I thought about adding the hydroxyl hydrogens, but I'm honestly not sure where to put them. My first thought was to make a "round robin" set of hydrogen bonds within each set of three hydroxyls, but one could also point the hydrogens outwards to make hydrogen bonds with the equidistant lone-pair of the nitrogens. What do you think?

Warm regards and warm mice for k, Willow 16:16, 3 November 2006 (UTC)

I don't know, the model is very nice and regular, but especially the space-filling model just seems to be saying "Ow, my hydrogens!" I know everything is obvious in hindsight, but I'm still surprised at how many people expected proteins to have a regular and symmetrical structure - and most of all, a regular and symmetric structure in common - considering the diversity of things proteins do.

On where to put the hydroxyl hydrogens... I think I take my suggestion back. I think the only reason I keep seeing them as carbonyls is that I spend too much time looking at real proteins, so this is probably less of a concern than I thought for the average reader. The three-way 'round robin' hydrogen-bonding pattern exists in water clusters, so it might be somewhat favored in water, but I kind of think that choosing one or the other representation might confuse readers, who could think that the hydrogen arrangement was part of the cyclol model. Opabinia regalis 04:17, 7 November 2006 (UTC)

Hi, O, you're right; the steric clashes are the most damning part of the cyclol model a priori, and I don't think Wrinch ever really gave an adequate answer on that topic. But just imagine how cool it would be if the elementary charge were only ~25% larger, a nice even 2x10^-19 C — cyclol proteins galore! ;)

I'll try to make a diagram of the modern cyclols tomorrow and fill in that section more. Is there anything else you'd recommend before submitting it for peer review? Thanks again for your help! Willow 20:15, 7 November 2006 (UTC)

Sorry I didn't get back to this too quickly - the only text thing I can think of that's likely to stand out is the presence in the "see also" section of items that have already been wikilinked in the text. (IMO this is a silly guideline, but there it is.) The reaction image is nice but might be better with the three molecules arranged linearly, so there's not a blank white space in the lower right? I'm not sure how wide that would look on some screens, though. Opabinia regalis 04:08, 11 November 2006 (UTC)

[edit] Peer reviewer output

The following suggestions were generated by a semi-automatic javascript program, and might not be applicable for the article in question.

• Consider adding more links to the article; per WP:MOS-L and WP:BTW, create links to relevant articles.

Cyclol is linked from most relevant articles, such as protein and primary structure. Being an obsolete theory, it will be found mainly under the "History" section of protein-science articles.

• Per WP:MOSNUM, please spell out source units of measurements in text; for example, the Moon is 380,000 kilometres (240,000 mi) from Earth.

Added links to all units in the article.

• Per WP:MOS#Headings, headings generally should not repeat the title of the article. For example, if the article was Ferdinand Magellan, instead of using the heading ==Magellan's journey==, use ==Journey==.

Removed "cyclol" from all section headings.

• Please reorder/rename the last few sections to follow guidelines at WP:GTL.

Moved "See also" ahead of the References; was there something else?

• This article may need to undergo summary style, where a series of appropriate subpages are used. For example, if the article is United States, than an appropriate subpage would be History of the United States, such that a summary of the subpage exists on the mother article, while the subpage goes into more detail.

I feel that the unity of the subject matter is best served by a single article, especially since it is obsolete theory of protein structure. The modern cyclol molecules could perhaps have their own article, but that is only one section of the entire article.

• There are a few occurrences of weasel words in this article- please observe WP:AWT. Certain phrases should specify exactly who supports, considers, believes, etc., such a view. For example,
  • correctly
  • might be weasel words, and should be provided with proper citations (if they already do, or are not weasel terms, please strike this comment).^[1]

I don't see the weasel words — would you please be more specific?

• As done in WP:FOOTNOTE, footnotes usually are located right after a punctuation mark (as recommended by the CMS, but not mandatory), such that there is no space inbetween. For example, the sun is larger than the moon [2]. is usually written as the sun is larger than the moon.[2]

As far as I can tell, I did this correctly.

• Please ensure that the article has gone through a thorough copyediting so that it exemplifies some of Wikipedia's best work. See also User:Tony1/How to satisfy Criterion 1a.

The exposition seems reasonably coherent and organized chronologically.

You may wish to browse through User:AndyZ/Suggestions for further ideas. Thanks, Wim van Dorst (Talk) 00:16, 9 November 2006 (UTC)

Additionally, may I recommend that for a chemical such as cyclol, the infobox to use is the {{chembox}}. Read about it on wikipedia:Chemical infobox. Wim van Dorst (Talk) 00:16, 9 November 2006 (UTC).

A cyclol is a reaction and a family of compounds (like "alcohol" or "ketone") so it seems hard to make the usual chembox. The cyclol fabric and cyclol molecules predicted by Wrinch have not been observed at all, so it would be difficult to give any parameters for them. Similarly, the SMILES format might be hard-pressed to describe a cyclol fabric.

I hope this answers your criticisms; thanks for your help in making the article better! :D Willow 23:12, 10 November 2006 (UTC)

[edit] Proposal for new "scientific method section"

The cyclol model of globular protein structure is an interesting example of the role of hypotheses in developing a scientific theory. As a hypothesis, the cyclol model was not revolutionary: it lay completely within the generally accepted basis (paradigm) of natural product chemistry at the time, notably the confidence that the structures of biological molecules, even the most complex, obey the general priniciples of physics and chemistry. However the hypothesis showed an unusual simplicity and generality of application, which made it attractive to other scientists.

It has been argued that the cyclol hypothesis should never have been advanced,[84][85] because of its a priori flaws, e.g.,

• it does not accommodate proline in protein structure;
• the cyclol reaction is (supposedly) thermodynamically disfavored ; and
• the high lateral density of the cyclol fabric is inconsistent with known repulsion between non-bonded atoms.

These criticisms are somewhat anachronistic. The cyclol model cannot accomodate proline in its simplest form, but neither could any other model of a regular arrangement of amino acid residues. It is now accepted that proline residues cause a change in the structure of the peptide chain from regular packing (α-helix or β-pleated sheet) to a less regular structure: similar minor modifications of the cyclol model would have been sufficient to account for the observation of proline in proteins. The cyclol reaction is thermodynamically disfavored in the gas phase, but Wrinch and Langmuir correctly predicted that it may be favored in solution, where solvation is both important and difficult to calculate.

The progress of the cyclol model also demonstrates, both by its proponants and its opponants, a well-known problem with falsificationism. The cyclol hypothesis could be (and was) falsified, but the techniques necessary for its falsification required a certain confidence in the theoretical background of other models which were still in their infancy, such as X-ray crystallography, molecular spectroscopy and the various theories of chemical bonding, and in their application to small quantities of complex biological molecules. These problems in the interpretation of experimental and calculational results explain in part the long survival of the hypothesis. On the other hand, the rejection of covalent bonding in favor of hydrogen bonding as an explanation of protein structure, championed by Pauling, led to the neglect of the role of hydrophobic interactions for many years.

The legacy of the cyclol model was the general acceptance that the observed density of globular proteins implied that their structure be, at least in part, regular: this came to be known as the secondary structure of proteins. Such regular structures are much more amenable to analysis by X-ray crystallography, particularly given the meagre computing resources which were available at the time. The development of crystallographic techniques, promoted by the study of the cyclol model, led to the identifcation of α-helices and β-pleated sheets, and to the elucidation of the structure of DNA. The description of the tertiary structure of proteins required greater developments in techniques and in calculational methods: the first such structure to be described was that of insulin in 1967, more than thirty years after the development of the cyclol model.

[edit] Comments

I tentatively propose the above as a replacement for the current scientific method section, which I feel doesn't do justice to the various differences of opinion as to what, exactly, the scientific method is. I haven't replaced the existing section, because I feel that the above will need some editing, and maybe expansion. All the same, I hope it can provide a framework for improvements in this area. Physchim62 (talk) 14:39, 17 November 2006 (UTC)

Hi, Physchim62, thanks for your hard work and thoughts on making Cyclol more accurate and expressive. Please forgive my delay; I've been trying to familiarize myself with the basic arguments in the field. Unfortunately, I also see from your draft that I failed to convey several salient points of the cyclol history; if you don't understand, then I'm sure few others will. :( I was trying to be delicate and respectful of the people involved, but I seemed to have sacrificed clarity. My family is still visiting for Thanksgiving, but I'll begin work again on Monday; please be patient — thanks! Willow 13:37, 25 November 2006 (UTC)