User:ElNando888/Switch Cloud Labs/Chirality

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Revision as of 18:24, 8 June 2013 by ElNando888 (talk | contribs) (work in progress, first chapter about the unbound state)
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== Introduction ==

The first round of the Switch Cloud Labs was rich of surprises. I would put among the most interesting experimental results, the general failure in Lines by Satrryjess and the intrguing SHAPE data obtained in Chirality by kcabral28. I'd like to develop on the latter, and while I'll focus on the top-runner design, Brourd's Chirality - Sub 3 (unstable), I believe that the ideas presented below may very well apply to the vast majority of designs submitted in that lab.

 

== The unbound state ==

Blog is 3.png

At first sight, nothing looks strange in this design, but on a closer look on the terminal stacks, one can notice a few details.

<tbody> </tbody>
Blog is 10.png Blog is 12.png Blog is 11.png
Not overly stable Simply unstable Potentially stable

From these pictures, one may conclude that for both stacks to form, they basically had to do so simultaneously. Which would not be so unlikely, if the loop was symmetric, but with this difficulty added, the possibility seems quite remote to me...

Which is why I tend to believe in another hypothesis, which has the additional advantage to explain some of the experimental data directly. Check this out:

Blog is 14.png

This is also potentially stable, and there are no problems with simultaneity, since it's a single stack. Placed in context, this gives:

Blog is 7.png

The advantage I was talking about, is simply that this structure is fully consistent with the absence of SHAPE signal between bases 46 and 55. 

You are probably going to object that this doesn't explain the signals around 22-24 and 29-34. Well, indeed, I don't have a solid explanation for those, but I do have a conjecture, supported by a simulation cooked by RNAComposer. Of course, RNAComposer's simulations don't have the same value as solved structures, like those found in PDB, but one could say that its depiction of stacks is probably very close from reality, while its generated loops (those that don't match precisely a fragment found in PDB) are well-educated guesses.

This said, please observe that a hook is actually a wine bottle opener, and that a hairpin loop has nothing to do with a balloon.

The stackish blob that turns magenta, yes, that's the hairpin loop.

The second spin with volume added is meant to illustrate that:

  • there may be tertiary interactions between bases in the loop and the neighboring stack
  • and even without interactions, the proximity of the structures may make it very difficult for the SHAPE reagent to reach some of the binding points on the riboses, making those bases appear as protected, while there aren't actually paired.

 

== The bound state ==

(coming soon)