The Strategy Guide to solve EteRNA Puzzles

  • 38
  • Article
  • Updated 11 months ago
Let's discuss useful strategies require to solve EteRNA challenge puzzles .
Photo of Snehal (Neil) Gaikwad

Snehal (Neil) Gaikwad, Alum

  • 25 Posts
  • 9 Reply Likes
  • excited

Posted 9 years ago

  • 38
Photo of Matt Baumgartner [mpb21]

Matt Baumgartner [mpb21], Alum

  • 128 Posts
  • 33 Reply Likes
mpb21's strategy guide for solving EteRNA puzzles


Effect of Energy:
When considering energy, lower is generally better. There is a box which has the total energy (in kJ - kilojoules

See this article about free energy as it applies to EteRNA:

Orientation of the pairs:
Also the orientation of the pairs is important. In a stack, a G-C pair is not (generally) equivalent to a C-G pair.

Basic Strategy
My strategy for solving the EteRNA challenge puzzles is as follows. This strategy should work for puzzles of all difficulty levels.

-Step 1:
Fill all stacks with AU pairs of random lengths of 1-3. There are several things to be aware of when doing this to pay attention to that will be discussed later in the advanced strategies section below.
-Step 2:
Replace AU pairs with GC pairs as needed to stabilize structure into desired shape. Use as many as needed to stabilize it REGARDLESS of the number of allowed GC pairs.
-Step 3:
Once the structure is stabilized, go through the GC pairs and remove as many as needed to get under the number (if applicable). This is generally the hardest part in the more difficult levels. One good and quick way to start is to change each of the GC pairs to GU pairs and see if it maintains the structure. This will quickly remove some of the extra GC pairs that were placed earlier.

Next, if you still need to reduce the number of GC bonds, what you can try is to change the GC pairs to AU pairs, which are the next strongest bonds. Be sure to try the AU pair in both orientation (i.e. AU and UA) because they are not always of equal strength.

-Step 4:
Start on one end of the molecule (or anywhere, it doesn't matter) and change the A of EVERY AU pair into a G. Check to see if the structure is still in the target shape (ring around structure icon stays white). If it maintains the structure, keep it and move on. If not, undo (press Z key) and move on.

-Step 5:

Advanced strategies

There are several things to pay attention to when completing the levels (especially the harder levels)

When placing the AU pairs in Step 1, there is several things to consider.
First: GU-UG stacks are not generally stable. Meaning the if the stack contains alternating GU stacks, it will probably not be stable
For example: The stack

Is generally not stable, where N stands for any nucleotide (although it is possible to stabilize it by changing the flanking nucleotides (N here)).

Thus, when you are placing the AU pairs in Step 1, having perfectly alternating AU pairs is not a wise strategy because it will limit the number of GU pairs you can place in Step 4. Therefore placing AU lengths closer to 3 or sometimes 4 may be better

The reason that the lengths should be "random" or at least not in a repeating pattern, is so that the sequence of one side of the stack is specific to binding to the other side of the stack and no other stacks or loops

In some puzzles there are some loops that can be particularly difficult to keep closed. For example, in the Saccharomyces Cerevisiae puzzle, the top most loop is often very difficult to solve. The loop is structured as a loop closed by a two pair stack

Putting two GC pairs in the stack is not sufficient to keep the loop closed. So the way to keep it closed is by modifying the nucleotides adjacent to the stack in the loops.

For example, in the Saccharomyces Cerevisiae puzzle, putting two G's in positions adjacent to the loop, stabilizes the stack and keeps the loop closed.


This sort of technique is also applicable to other types of loops as well. If you are having problems getting loops to close, try changing some of the nucleotides in the loop to G and see if it helps the free energy.

Good Luck!

If you are having trouble with loops, check out the Loops Guide:
Photo of Ted Laurent

Ted Laurent

  • 1 Post
  • 0 Reply Likes
Thank you for taking the time to write this guide!
Photo of mummiebrain


  • 26 Posts
  • 3 Reply Likes
I use exactly the same strategy - developed by trial and error. It would be good if we could see our solution after the fantastic winning display is finished. I often can't remember exactly what I've done to win.
Photo of catwings


  • 1 Post
  • 0 Reply Likes
Thank you! Now that the puzzles do let you do this, I wouldn't want to live without it.
Photo of Snehal (Neil) Gaikwad

Snehal (Neil) Gaikwad, Alum

  • 25 Posts
  • 9 Reply Likes
While solving puzzles, you might have encountered Unpaired Bases as shown below. You can use strategy 1 or strategy 2 to fold an RNA into target mode.

Photo of dimension9


  • 186 Posts
  • 45 Reply Likes
This is a key point, sneh! Many thanks for stating it in such an explicit, focused - and illustrated - manner - This broke me through in several puzzles that were giving me a tough way to go.