[Strategy Market] [Switch] Elements: Obligatory switching base pairs in MS2/FMN switches


As a rule of thumb the obligate switching base pairs in a MS2/FMN switch are following:

  • The 3 base pairs after the switching end of the aptamer are mandatory, since they needs to be filled to make a legal solve in the energy model. These 3 bases needs to be forming in the one state, but breaking in the other.

  • Also the 7 base pairs of the MS2 hairpin are obligatory. The MS2 needs to be breaking in one state and forming in the other.

So that’s 10 base pairs all in all.

By switching base pairs I mean base pairs that are not going to stay the same between the two states. Each state can have a different amount of actual switching base pair. Like state 1 may have 10 base pairs that are involved in the switching, but in state 2 there may actually be 12 base pairs involved in the switching. So by obligate switching base pairs I’m trying to hit down on those that needs to get moving anyway.

Now all the base pairs in the MS2 hairpin don’t always need to be switching - as it is sometimes enough that just a few of them break open - so the actual switching number can be lower. But that’s fairly okay.

But generally most of the top scoring switches have their number of actual switching base pairs very close to these 10 base pairs. Not much above or much below. That is if the switch is a partial and not a full moving switch or have a full moving aptamer. So it is possible getting a switch moving with more base pairs, but I still consider it harder to get a well controlled switch with the whole switch moving. So this is the motivation behind the strategy.


I wish to give bonus to designs that keeps the amount of switching base pairs at a minimum, and increase penalty for designs that has huge amount of base pairs switching. This goes for both turn on and turnoff labs. Either state included.

  • I wish to reward all designs that has the obligatory amount of 10 switching bases or less.

  • Slightly decrease reward for designs that has up to 12 switching base pairs

  • For designs that has more than 12 switching base pairs, start penalize and increase penalty it as the number goes higher.

MicroRNA’s are excluded since they obviously :slight_smile: needs a bigger amount of switching base pairs due to need to switch between no microRNA in one state and pairing up with most of a 22 nucleotide long sequence in next.


In exclusion labs there tends to be a bit fewer base pairs in the second state than the 1. But instead of accounting for that here, I will write another strategy that should take care about the differences in switching base pairs between the states.

Background articles

Different types of switches

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Dear Eli Fisker, 

Your strategy has been added to our implementation queue and we should have it completed within the next two to three weeks. You can check the status of the implementation here.

We will also be uploading the code used to write your strategy on this page if you are interested in reading it later.

After implementing your idea, we will post the direct link to the code here. Then, we will then optimize the parameters, and test it. At that point, we will tell you the correlation of how good your strategy was and what the new optimized parameters are.

Thanks for sharing your idea!

Vineet Kosaraju
The EteRNA Team

Dear Eli Fisker,

I am pleased to announce that a preliminary version of your strategy has been implemented with 14 lines of code. The code might slightly change in the future to remove bugs, but you can check the current version here. We will soon work on optimizing your parameters and testing the strategy.

Thank you again for sharing your switch strategy!

Vineet Kosaraju
The EteRNA Team

Eli, I looked at Vineet’s coding of your strategy and realized that there are a number of different ways your general idea might be reduced to an algorithm.

Here’s an example:

Would you say the switching base pair count is 2, because two of the base pairs in state 1 are broken up in state 2?  Or 3, because three of the pairs in state 2 are broken up in state 1?  Or 5, because it is the sum of the two? Or something else?  For example, I can see a case for counting switching bases instead of switching base pairs, in which case I would count 8 bases (the ones I’ve circled) as switching.  Dividing by 2, this could be given a “pair” count of 4. 

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Hi Omei and Eli Fisker,

When implementing the strategy I was also thinking of these different possible base pair definitions, and I just randomly chose the first one. Let me know which one you think best fits the strategy and I can modify the code :slight_smile:


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Hi Omei and Vineet!

Omei, big thx for making me aware of the various outputs of my strategy and big thx Vineet, for your questions also.

My apologies for the unclarities. I was counting base pairs in obligate switching areas, across both states at once. So I was counting the 3 base pairs at the switching end of the aptamer,  would be as obligatory for switching between both states - as they would be moving cause while being on in state 2, they would be off for state 1. So these 3 base pairs would be involved in switching no matter what. (In exclusion/turnoff labs).

Similar for the MS2 hairpin. While being on in state 1, but off for state 2, part of it would still need to be switching. So 7 base pairs - while not all are always needed to get moving -  like they were not in the example you showed, Omei.

So the example image holds 3 switching aptamer base pairs between states, but only 2 switching base pairs for the MS2 - as the last 5 are not breaking in the estimate.

10 obligate switching base pairs across both states and 5 actual switching base pairs.

Also for this lab have the area for obligate switching bases overlapping since the forming MS2 and forming aptamer are sharing some bases.

In this exact example there are fewer actual switching base pairs than what would be possible if both all aptamer base pairs and MS2 base pairs move. In this example you posted, Omei, I count 5 obligatory switching base pairs. (I think that is about minimum possible, perhaps 4 will fly somewhere.) But it is still okay, since several high scoring designs get away with this. My strategy only wants to get angry, if there are way too many switching base pairs compared to maximum obligatory switching base pairs at 10 obligatory switching pairs.

Similar for the Same state labs, where the aptamer and MS2 is on in one state and off in the other. Those would also have the 3 obligate switching pairs (although in practice there can be more - there regularly are 4-5 base pairs involved in the switching end of the aptamer) aptamer base pairs break + the MS2 hairpin base pairs.

Counting across states

So I have been counting across states. Not in single states alone. This is to cover up for which ever way the switch direction is and if aptamer and MS2 is in same or different states. Plus I found that having around 10 switching base pairs give or take a little, would cover for most of the successful switches. Where having a lot more switching base pairs - obligatory and especially if not in most cases are a bad idea. Except for the few lucky full moving switches.

What I should have called it

So I think what I should have called obligatory switching base pairs this instead: obligate switching base area, to lessen confusion. So all bases in the area of almost obligate switching - like aptamer closing and MS2 base - counts as obligate switching bases - bases that would almost always be involved in switching in some way. Even though not all of them will be bound up and involved in active switching.  

Then bases that get involved and pairing up with these bases from the obligate switching areas, could be counted as different. They are still involved in the switching, but do not origin from the obligate switching area.

Obligate switching area (Orange) + Additional switching bases (black rings)


Notice the black ringed area. In this case the only other bases involved in the switch, are the MS2 turnoff bases. These are really important. As they make the switch happen. By both binding strongly with the first part of the aptamer sequence (FMN1) in state 1 and turning off the MS2 in state 2. The MS2 turnoff sequence have similarities across the turnoff labs, and often even in base content. (CU segment) (Link to background post)

Generally I think there needs to be more obligate switching bases (counting only the bases involved in actual switching = pairing) than additional switching bases.

So this was what strategy I originally intended and what I would want. (Variation A) But I wish to keep the strategy that you already programmed, Vineet, as an extra variation B, as I would like to see how it does too. Also I’m also very interested in the variation C, that Omei mentions:

For example, I can see a case for counting switching bases instead of switching base pairs, in which case I would count 8 bases (the ones I’ve circled) as switching.  Dividing by 2, this could be given a “pair” count of 4.

One of these 3 strategies will hit closer to home, so I would like to not rule them out beforehand. So can I get variation A, B and C? :slight_smile:

Sure Eli, I’ll code up the variations. I’m really interested in which variation will be more accurate (and why) :slight_smile:


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Vineet, sweet! :slight_smile:

Dear Eli Fisker,

I am pleased to announce that preliminary versions of the three variations of your strategy have been implemented. Please note that the code might slightly change in the future to remove bugs.

Variation A: Implemented with 22 lines of code.
Variation B: Implemented with 19 lines of code.
Variation C: Implemented with 21 lines of code.

We will soon work on optimizing your parameters and testing the strategy.

Thank you again for sharing your switch strategy!

Vineet Kosaraju
The EteRNA Team

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Big thx, Vineet! :slight_smile:

Special thx to Omei for catching that the strategy was not doing as I intended. And thx to you both for making strategy variations.