For an FMN switch, reward designs that keep one of the two closing stems fixed (i.e paired the same way) in both states of the switch.
Tie the knot on the one end of the aptamer that is not needed for the switching area anyway. Its one of the safest way to controlling a design, so it doesn’t turn into a full moving switch and gets far harder to solve than necessary.
I have only found a minority of designs that really need to have the aptamer moving at both ends, and I suspect it relates very much to that the MS2 sequence being so far from the FMN aptamer sequences, so it was the only way to raise entropy enough to get the switch moving - as a last resort before going full moving switch.
As soon as there are something like 12 (and of cause more) bases between the 2 aptamer sequences, I think it will start pay off tying a knot at that end of the apatmer. Something that EternaBot didn’t always do in its solves, despite there being 17 bases between the aptamer sequences. This caused more than needed of the designs, into full moving switches.
In some cases EternaBot, did attempt to make a stem (It had to do the 3 base pair stem to make a legal solve. )
But what it regularly failed to do and what we do more routinely is make that stem longer. As what often happened was that the too short Aptamer closing stem, were so weak that it easily broke and allowed the whole design to turn into a full moving switch.
Its always harder to a whole bunch of base pairs switch as wished, compared to a smaller amount of base pairs.
For each base pair this fixed stem is longer than the obligatory 3 base pairs, give + 1.
Up till 7 base pairs.
If the stem is longer than 7 basepair, give +1 for each GU added per 5-6’th base.
Also reward if an internal loop break up the stem from being longer than 7 bases.
As I play with the latest round of labs I’m not so sure on this one. However we could check it against the lab results by running the numbers.
The real pro to this strategy is the significant decrease in search space that a player has to go through in order to design a solution for a puzzle. However, as seen by sequences submitted by ViennaUCT, successful riboswitch designs can take on many forms.
The main difficulty is optimizing designs for kinetics and ensemble interactions, both of which can be difficult to do by hand. Now if only there was some current way for players to code tools to do this stuff within the applet in real time…
FoldIT has a scripting mode within their game that makes it possible to script actions. In their case it is mostly shake, wiggle, etc, but it is an interesting idea. Something to bring up at EternaCon perhaps.
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!
The EteRNA Team
I am pleased to announce that a preliminary version of your strategy has been implemented with 40 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!
The EteRNA Team