Does RNA naturally want to tangle itself? Thoughts on ideal configurations of switches.

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Does RNA naturally want to tangel itself? I have been analyzing the OpenTB results and have found that switches tend to like to have a nice long static stem in them and only have other segments switching kinda like a squid in the 2 state designs. In the 4 state designs I have found that this carries true but the best switches have some designs that are a bunched up ball that releases into a long stems. The bunched up ball is static though in the 1st 3 states. This is where I get to my question about whether RNA likes to tangel itself. I wonder if teh bunched up version will switch back adn forth easily compared to the designs were the 4th state just swapes out oligos in teh long static stems and maybe changes the static stem just alittle bit but not significantly. If RNA likes to naturally tangle itself then maybe those tangled designs will do better since there is alot of potential built up energy waiting to release and then when the 4th state oligos are removed the designs fales back into a ball easily. Or are both configurations just as good... The ones where the 4th state is just the long static stem in the first 3 states with swapped out oligos in the 4th state could switch very easily and be very strong at the same time since there is a small amount of collapse with hairpins forming and whatnot and squishing when switching between the 3rd and 4th state to accommodate the different oligos. I think that RNA behaves in a very mechanical way.

Respectfully,
Jennifer Pearl
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Jennifer Pearl

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Posted 2 years ago

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Eli Fisker

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@Jennifer, I really like what you have been up to.

That squid image for entanglement is a great mental image.

I think you are onto something. I am wondering though if instead of the 4th states being unentangled and the 1-3 state being entangled, a slight change of story is taking place.

If one sort the designs after global fold change instead of "local" fold change and group the designs in to states of ON or OFF, a different trend is starting to emerge.

Example from the hard labs and the design with best global fold change.





Sum up

- OFF states tends towards entanglement
- ON states tends towards unrolling
(Edited)
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Jennifer Pearl

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Can you explain what you interpret as entanglement and unrolling? I can kinda see what you mean looking at the designs in the UI but I am having trouble. 
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Eli Fisker

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Sure.

When looking at both the hard labs, the designs with high global fold change tends towards having more of their parts entangled - folded together in their OFF states. Like more more parts hidden away in hairpins.

Hiding reporters and such as hairpins stems or as hairpin loops are a good way of getting things shut off. Or inputs binding sites hidden the same way.

For ON states of both the hard labs, the designs tends towards having inputs unrolled - opposite entangled - with more inputs bound up and less sequence hidden away in switching stems.

ON states can have switching hairpins too, but they tend to have fewer.

Perhaps unentangled is a better word than unrolled?

Also one thing I did not clearly get explained and illustrated. Some of the stems in the hard INC designs are not included as folded up stems as they are not directly part of the switch as they are static. I have now got one I missed drawing added, and have highlighted them with blue color.

Now it should get clearer that the OFF states have more switching hairpins - hidden sequence.



ON switches generally use less of the sequence, compared with OFF switches. Instead they hide their excess bases in a static stem or two at end position/s.

Hope this helps
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Jennifer Pearl

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I understand now. I looked at the designs again and I see what you are talking about very distinctly in the hard INC labs. It is a little harder to see in the hard DEC lab. In the hard DEC lab it seams less drastic. I wonder if it is something that is more true for the INC labs than the DEC labs? I do like the concept of using hairpins to hide parts of the sequence.
(Edited)
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Astromon

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Hmm rereading this makes me think of this entanglement in the off state to hide reminds me of the way DNA folds itself to hide from water to sort of keep better. 
and uses the letter T instead of U. With this concept its hiding things to stay in the off position. 
(Edited)
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Astromon

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I would like to see a screen shot of a squid-like structure. 
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Astromon

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I would like to say the three states balling up and rolling out at the last state and it doing it for energy reasons and others is interesting! Thanks