From the dot plots produced by ViennaFold 2.2 for the ON and OFF state, pull the probability of the pair forming at the base of MS2 hairpin. Here’s a picture to illustrate the pair, but the exact base numbers will depend on where the hairpin is in the submission.
If the probability in the ON state is below a threshold TBD, deduct a penalty. If the probability in the OFF state is above a (different) threshold, deduct a different penalty. Presumably, these thresholds and penalties will need to be calculated independently for the switch direction and type of aptamer (MS2 vs miRNA).
My expectation is that this will be useful for weeding out some poorly scoring designs, but not particularly useful for distinguishing great designs from mediocre ones. Thus, the most effective thresholds will probably be fairly tolerant ones.
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.
I am pleased to announce that a preliminary version of your strategy has been implemented with 17 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.
