Explanation Request: why does symmetry in internal loops have lower energy than similar, but smaller, sized asymmetric loops?

Gameplay and Strategies
1

Is there a 3D or other explanation why the energy model for similar sized loops gives lower energy for a symmetric loop?
For any (N+1) to N loop the energy is higher than a (N+1) to (N+1) loop.
Similarly, “same sized” loops benefit from symmetry (3-3 loop having lower energy than a 4-2.)
Lroppy asked in chat and none of us knew why.

(example using all unpaired NT’s as A and loop closed by AU pairs on both ends)
One might expect a 2-3 loop to have lower energy than a 3-3, but it doesn’t (3.7 vs 3.4)

1-1 1.7
1-2 3.9
1-3 4.1
1-4 4.7

2-2 2.8
2-3 3.7
2-4 4.4
2-5 5.1

3-3 3.4
3-4 4.1
3-5 4.7
3-6 5.3

2

Thank you for posting this. You should feel good. Here, have some karma

3

I think it’s quite simple: in symmetric loops, the bases have a good chance to actually form non-canonical pairs and more importantly, the stacking is conserved and the helix keeps “going on a straight line”, all these factors have a weak stabilizing power, but they accumulate to make for a tangible bonus.

In asymmetric loops, even if some non-canonical pairs form, there will always be at least one of them that must bulge out of the alignment, one way or the other, probably breaking the helix pattern and the chain of stackings, factors which contribute to destabilize the shape.

Feed your sequences into RNAComposer for instance, and observe in Chimera the resulting 3D simulations, you will be able to see what I’m talking about.

4

Another way to think of it, the symmetric loop has two equal lever arms holding it open, the asymmetric loop has a short arm that must work harder to do its job. It’s both a conformational strain effect and a matched/unmatched bonding effect.