UG multiloop stabilizer

I bumped into this yesterday, while trying to start to solve a puzzle.…

For some reason AU pairs in the middle won’t give any stability, but the UG pairs do.
Can anyone explain that to me?

is that repetition ?

Eli’s tricks guide has a section that deals with GU pairs in adjacent stack multiloops.


Yes, i recently saw that.
I was wondering more for a somewhat ‘scientific’ approach on why that is happening.

When solving puzzles, your goal is to make a sequence whose minimum free energy structure is equivalent to the target structure. The loop in your example makes a large positive contribution to free energy, but its formation is more than offset by negative contributions elsewhere.

A more intuitive way of thinking about it is to consider the alternative structures that your sequence could fold into. You want them all to be less stable - or higher in energy - than your sequence folded into the target structure.

For example, consider what happens if you open all of the closing GU pairs in the example you posted. Formation of a larger multiloop decreases free energy, but only by 2.1 kcal. The loss of the three GU pairs increases free energy by 4.1 kcal. The net change in free energy is positive, so the MFE structure contains the higher energy loop.