The Triloop Problem

As reported in this Google Document, currently the only way to form a triloop without using a GC pair to close it is to place two AU pairs in a certain way. But in nature, other triloops form (as reported in the same document). So the problem is that eteRNA discards perfectly acceptable triloops because of its parameters.

The engine that folds the RNA needs to be tweaked so it can recognise such triloops as folded. Immediately.


EteRNA needs to keep the process for selecting player designs constant while data is gathered for the paper. That’s why they haven’t changed the voting system. I imagine the same reasoning applies to changing parameters. Also, it raises the question of what new parameters to use. This paper might be a start - but I don’t know the validity of just throwing in a new way of representing triloops.

Finally, some of those triloops I listed are possibly stabilized by the tertiary structure of the RNA. That’s especially true with a lot of the lonepair triloops. I don’t know how they could account for that or re-create it in EteRNA at the moment. You might find Rhiju’s reply to my noncanonical base pair thread useful as well, since that thread was kind of getting at the same concept - situations in which EteRNA’s way of representing RNAs breaks down.

Something interesting for the devs might be creating a “sandbox mode” where players could solve / design using custom parameters. Eventually it could be carried over into lab when more synthesis slots become available.

BTW, I solved a puzzle yesterday with the sequence 5’-CUGXXXUAG-3’ creating a triloop. Brourd’s “RNA Warrior” has a lonepair triloop on a very large loop. But yes, our options are limited.

Yes, as you pointed out, the engine that folds the RNA is imperfect. If fact as we have seen from the lab results, it is sometimes down right awful. This is actually the very reason that this eteRNA project exists. As is, the folding algorithm is very complex and modifying it is very challenging.